Publications by authors named "Kenneth B Storey"

499 Publications

The naked truth: a comprehensive clarification and classification of current 'myths' in naked mole-rat biology.

Biol Rev Camb Philos Soc 2021 Sep 3. Epub 2021 Sep 3.

Department of Otolaryngology, Johns Hopkins School of Medicine, Baltimore, MD, 21205, U.S.A.

The naked mole-rat (Heterocephalus glaber) has fascinated zoologists for at least half a century. It has also generated considerable biomedical interest not only because of its extraordinary longevity, but also because of unusual protective features (e.g. its tolerance of variable oxygen availability), which may be pertinent to several human disease states, including ischemia/reperfusion injury and neurodegeneration. A recent article entitled 'Surprisingly long survival of premature conclusions about naked mole-rat biology' described 28 'myths' which, those authors claimed, are a 'perpetuation of beautiful, but falsified, hypotheses' and impede our understanding of this enigmatic mammal. Here, we re-examine each of these 'myths' based on evidence published in the scientific literature. Following Braude et al., we argue that these 'myths' fall into four main categories: (i) 'myths' that would be better described as oversimplifications, some of which persist solely in the popular press; (ii) 'myths' that are based on incomplete understanding, where more evidence is clearly needed; (iii) 'myths' where the accumulation of evidence over the years has led to a revision in interpretation, but where there is no significant disagreement among scientists currently working in the field; (iv) 'myths' where there is a genuine difference in opinion among active researchers, based on alternative interpretations of the available evidence. The term 'myth' is particularly inappropriate when applied to competing, evidence-based hypotheses, which form part of the normal evolution of scientific knowledge. Here, we provide a comprehensive critical review of naked mole-rat biology and attempt to clarify some of these misconceptions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/brv.12791DOI Listing
September 2021

Metabolic responses of plasma to extreme environments in overwintering Tibetan frogs Nanorana parkeri: a metabolome integrated analysis.

Front Zool 2021 Aug 28;18(1):41. Epub 2021 Aug 28.

School of Life Sciences, Lanzhou University, Lanzhou, 730000, Gansu, China.

Many animals lower their metabolic rate in response to low temperatures and scarcity of food in the winter in phenomena called hibernation or overwintering. Living at high altitude on the Tibetan Plateau where winters are very cold, the frog Nanorana parkeri, survives in one of the most hostile environments on Earth but, to date, relatively little is known about the biochemical and physiological adjustments for overwintering by this species. The present study profiled changes in plasma metabolites of N. parkeri between winter and summer using UHPLC-QE-MS non-target metabolomics in order to explore metabolic adaptations that support winter survival. The analysis showed that, in total, 11 metabolites accumulated and 95 were reduced in overwintering frogs compared with summer-active animals. Metabolites that increased included some that may have antioxidant functions (canthaxanthin, galactinol), act as a metabolic inhibitor (mono-ethylhexylphthalate), or accumulate as a product of anaerobic metabolism (lactate). Most other metabolites in plasma showed reduced levels in winter and were generally involved in energy metabolism including 11 amino acids (proline, isoleucine, leucine, valine, phenylalanine, tyrosine, arginine, tryptophan, methionine, threonine and histidine) and 4 carbohydrates (glucose, citrate, succinate, and malate). Pathway analysis indicated that aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, and nitrogen metabolism were potentially the most prominently altered pathways in overwintering frogs. Changes to these pathways are likely due to fasting and global metabolic depression in overwintering frogs. Concentrations of glucose and urea, commonly used as cryoprotectants by amphibians that winter on land, were significantly reduced during underwater hibernation in N. parkeri. In conclusion, winter survival of the high-altitude frog, N. parkeri was accompanied by substantial changes in metabolomic profiles and this study provides valuable information towards understanding the special adaptive mechanisms of N. parkeri to winter stresses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12983-021-00428-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403389PMC
August 2021

44 Current Challenges in miRNomics.

Methods Mol Biol 2022 ;2257:423-438

Medical Informatics and Bioinformatics, Institute for Measurement Engineering and Sensor Technology, Hochschule Ruhr West, University of Applied Sciences, Mülheim adR, Germany.

Mature microRNAs (miRNAs) are short RNA sequences about 18-24 nucleotide long, which provide the recognition key within RISC for the posttranscriptional regulation of target RNAs. Considering the canonical pathway, mature miRNAs are produced via a multistep process. Their transcription (pri-miRNAs) and first processing step via the microprocessor complex (pre-miRNAs) occur in the nucleus. Then they are exported into the cytosol, processed again by Dicer (dsRNA) and finally a single strand (mature miRNA) is incorporated into RISC (miRISC). The sequence of the incorporated miRNA provides the function of RNA target recognition via hybridization. Following binding of the target, the mRNA is either degraded or translation is inhibited, which ultimately leads to less protein production. Conversely, it has been shown that binding within the 5' UTR of the mRNA can lead to an increase in protein product. Regulation of homeostasis is very important for a cell; therefore, all steps in the miRNA-based regulation pathway, from transcription to the incorporation of the mature miRNA into RISC, are under tight control. While much research effort has been exerted in this area, the knowledgebase is not sufficient for accurately modelling miRNA regulation computationally. The computational prediction of miRNAs is, however, necessary because it is not feasible to investigate all possible pairs of a miRNA and its target, let alone miRNAs and their targets. We here point out open challenges important for computational modelling or for our general understanding of miRNA-based regulation and show how their investigation is beneficial. It is our hope that this collection of challenges will lead to their resolution in the near future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-0716-1170-8_19DOI Listing
January 2022

Role of MicroRNAs in Extreme Animal Survival Strategies.

Methods Mol Biol 2022 ;2257:311-347

Department of Biology, Carleton University, Ottawa, ON, Canada.

The critical role microRNAs play in modulating global functions is emerging, both in the maintenance of homeostatic mechanisms and in the adaptation to diverse environmental stresses. When stressed, cells must divert metabolic requirements toward immediate survival and eventual recovery and the unique features of miRNAs, such as their relatively ATP-inexpensive biogenesis costs, and the quick and reversible nature of their action, renders them excellent "master controllers" for rapid responses. Many animal survival strategies for dealing with extreme environmental pressures involve prolonged retreats into states of suspended animation to extend the time that they can survive on their limited internal fuel reserves until conditions improve. The ability to retreat into such hypometabolic states is only possible by coupling the global suppression of nonessential energy-expensive functions with an activation of prosurvival networks, a process in which miRNAs are now known to play a major role. In this chapter, we discuss the activation, expression, biogenesis, and unique attributes of miRNA regulation required to facilitate profound metabolic rate depression and implement stress-specific metabolic adaptations. We examine the role of miRNA in strategies of biochemical adaptation including mammalian hibernation, freeze tolerance, freeze avoidance, anoxia and hypoxia survival, estivation, and dehydration tolerance. By comparing these seemingly different adaptive programs in traditional and exotic animal models, we highlight both unique and conserved miRNA-meditated mechanisms for survival. Additional topics discussed include transcription factor networks, temperature dependent miRNA-targeting, and novel species-specific and stress-specific miRNAs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-0716-1170-8_16DOI Listing
January 2022

The effect of long-term cold acclimation on redox state and antioxidant defense in the high-altitude frog, Nanorana pleskei.

J Therm Biol 2021 Jul 30;99:103008. Epub 2021 May 30.

State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, China; School of Life Sciences, Lanzhou University, Lanzhou, China. Electronic address:

Cold hardiness is a key determinant of the distribution and abundance of ectothermic animals, and thermal acclimation can strongly influence stress tolerance phenotypes. However, the effect of cold acclimation on oxidative stress and antioxidant defenses is still not well understood. Here, we investigated the effects of long-term cold exposure (30 days at 4 °C in darkness versus 30 days at 20 °C in natural light) on the redox state and antioxidant defenses of the high-altitude frog, Nanorana pleskei, indigenous to the Tibetan plateau. We found that cold acclimation, under conditions mimicking winter, led to a significant increase in the ratio of oxidized glutathione (GSSG) to its reduced form (GSH) in liver and skeletal muscle tissues, suggesting that cold exposure induced oxidative stress in this species. Furthermore, malondialdehyde (MDA) contents were significantly augmented in heart, liver and muscle, indicating cold-related oxidative damage in these tissues. In the brain, GST activity, total antioxidant capacity (T-AOC), and vitamin C content showed a significant reduction after cold acclimation. In liver, an apparent decrease was also observed in the activities of SOD and GST, as well as T-AOC, whereas CAT and GPX activities showed a prominent increase in cold-acclimated groups. In kidney, there was a significant decrease in most antioxidant enzyme activities except for SOD and GST activity. In skeletal muscle, the activity of SOD, CAT, GR as well as T-AOC significantly decreased but GPX activity showed a significant increase in cold-acclimated frogs. These findings indicate that, in general, cold acclimation induces a suppression of the antioxidant defense system. Overall, our present study systematically describes the responses of antioxidant defenses to long-term cold acclimation and these findings contribute to extending the current understanding of the mechanisms of cold tolerance in high-altitude frogs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtherbio.2021.103008DOI Listing
July 2021

Functional and post-translational characterization of pyruvate dehydrogenase demonstrates repression of activity in the liver but not skeletal muscle of the Richardson's ground squirrel (Urocitellus richardsonii) during hibernation.

J Therm Biol 2021 Jul 15;99:102996. Epub 2021 May 15.

Institute of Biochemistry & Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, K1S 5B6, Canada. Electronic address:

Hibernation consists of a series of physiological and biochemical alterations in an animal that allows for reduced body temperatures down to near ambient levels and substantial fuel conservation allowing it to survive on stored fat supplies accumulated during the summer. The Richardson's ground squirrel is one such hibernator that undergoes such changes for as long as 9 months of the year. This study examines the role of regulation of the pyruvate dehydrogenase complex (PDC) during hibernation in the skeletal muscle and liver of the Richardson's ground squirrel. The current study demonstrates a great reduction in the activity of PDC in the hibernating liver, but not in the skeletal muscle. This was matched by a significant increase in the phosphorylation on a regulatory serine residue (S300) of the pyruvate dehydrogenase (PDH) E1α subunit. Examining the expression patterns of the relevant kinases for PDH and the associated phosphatase demonstrated some unexpected results. Specifically, an increase in PDKs 1 and 2 and a decrease in PDK4 was noted in the skeletal muscle tissue in response to hibernation and no alterations in the expression patterns of any of these enzymes were noted in the liver. This suggests that alternative modes of regulation of the kinases may be at play in hibernation to bring about the observed effects. Taken together this study demonstrates that PDH regulatory responses differ markedly between tissues and emphasize the importance of inhibition of the complex in the liver during hibernation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtherbio.2021.102996DOI Listing
July 2021

Epigenetic underpinnings of freeze avoidance in the goldenrod gall moth, Epiblema scudderiana.

J Insect Physiol 2021 Aug 17;134:104298. Epub 2021 Aug 17.

Institute of Biochemistry and Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada. Electronic address:

The goldenrod gall moth (Epiblema scudderiana) is a cold hardy insect that survives subzero temperatures during the winter by supercooling bodily fluids to approximately -40 °C, allowing the insect to remain unfrozen despite the freezing temperatures. This is characterized by a drastic increase of cryoprotectant glycerol along with widespread downregulation of non-essential genes and processes to conserve cellular energy. This study examined the role of epigenetic enzymes in regulating this freeze-avoidant process across a range of freezing temperatures experienced in nature. Cold and subzero temperature exposure in E. scudderiana resulted in upregulation of select DNA methyltransferase (DNMT) enzymes with concurrent decreases in DNMT activity and no change in activity of the Ten-Eleven Translocation (TET) demethylation enzyme activities. Levels of histone acetyltransferase (HAT) and histone deacetylase (HDAC) activity decreased during cold exposures. The increase in DNMT expression and concurrent decrease in HAT activity suggests a role for DNA methylation to assist with transcriptional suppression. These findings propose that epigenetic regulation of genes and histones underpin the winter survival strategies of this insect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinsphys.2021.104298DOI Listing
August 2021

MicroRNA-mediated inhibition of AMPK coordinates tissue-specific downregulation of skeletal muscle metabolism in hypoxic naked mole-rats.

J Exp Biol 2021 Aug 10;224(15). Epub 2021 Aug 10.

Biology Department, University of Ottawa, Ottawa, ON, Canada, K1N 9A7.

Naked mole-rats reduce their metabolic requirements to tolerate severe hypoxia. However, the regulatory mechanisms that underpin this metabolic suppression have yet to be elucidated. 5'-AMP-activated protein kinase (AMPK) is the cellular 'master' energy effector and we hypothesized that alterations in the AMPK pathway contribute to metabolic reorganization in hypoxic naked mole-rat skeletal muscle. To test this hypothesis, we exposed naked mole-rats to 4 h of normoxia (21% O2) or severe hypoxia (3% O2), while indirectly measuring whole-animal metabolic rate and fuel preference. We then isolated skeletal muscle and assessed protein expression and post-translational modification of AMPK, and downstream changes in key glucose and fatty acid metabolic proteins mediated by AMPK, including acetyl-CoA carboxylase (ACC1), glycogen synthase (GS) and glucose transporters (GLUTs) 1 and 4. We found that in hypoxic naked mole-rats (1) metabolic rate decreased ∼80% and fuel use switched to carbohydrates, and that (2) levels of activated phosphorylated AMPK and GS, and GLUT4 expression were downregulated in skeletal muscle, while ACC1 was unchanged. To explore the regulatory mechanism underlying this hypometabolic state, we used RT-qPCR to examine 55 AMPK-associated microRNAs (miRNAs), which are short non-coding RNA post-transcriptional silencers. We identified changes in 10 miRNAs (three upregulated and seven downregulated) implicated in AMPK downregulation. Our results suggest that miRNAs and post-translational mechanisms coordinately reduce AMPK activity and downregulate metabolism in naked mole-rat skeletal muscle during severe hypoxia. This novel mechanism may support tissue-specific prioritization of energy for more essential organs in hypoxia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1242/jeb.242968DOI Listing
August 2021

Insight into the Phylogenetic Relationships among Three Subfamilies within Heptageniidae (Insecta: Ephemeroptera) along with Low-Temperature Selection Pressure Analyses Using Mitogenomes.

Insects 2021 Jul 19;12(7). Epub 2021 Jul 19.

College of Chemistry and Life Science, Zhejiang Normal University, Jinhua 321004, China.

We determined 15 complete and two nearly complete mitogenomes of Heptageniidae belonging to three subfamilies (Heptageniinae, Rhithrogeninae, and Ecdyonurinae) and six genera (, , , , , and ). Species of Rhithrogeninae and Ecdyonurinae had the same gene rearrangement of CR, whereas a novel gene rearrangement of CR--NCR- was found in Heptageniinae. Non-coding regions (NCRs) of 25-47 bp located between and were observed in all mayflies of Heptageniidae, which may be a synapomorphy for Heptageniidae. Both the BI and ML phylogenetic analyses supported the monophyly of Heptageniidae and its subfamilies (Heptageniinae, Rhithrogeninae, and Ecdyonurinae). The phylogenetic results combined with gene rearrangements and NCR locations confirmed the relationship of the subfamilies as (Heptageniinae + (Rhithrogeninae + Ecdyonurinae)). To assess the effects of low-temperature stress on Heptageniidae species from Ottawa, Canada, we found 27 positive selection sites in eight protein-coding genes (PCGs) using the branch-site model. The selection pressure analyses suggested that mitochondrial PCGs underwent positive selection to meet the energy requirements under low-temperature stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/insects12070656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307263PMC
July 2021

Hypothermia promotes mitochondrial elongation In cardiac cells via inhibition of Drp1.

Cryobiology 2021 Jul 29. Epub 2021 Jul 29.

Cedars-Sinai Smidt Heart Institute, Barbra Streisand Women's Heart Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Hypothermia is a valuable clinical tool in mitigating against the consequences of ischemia in surgery, stroke, cardiac arrest and organ preservation. Protection is afforded principally by a reduction of metabolism, manifesting as reduced rates of oxygen uptake, preservation of ATP levels, and a curtailing of ischemic calcium overload. The effects of non-ischemic hypothermic stress are relatively unknown. We sought to investigate the effects of clinically mild-to-severe hypothermia on mitochondrial morphology, oxygen consumption and protein expression in normoxic hearts and cardiac cells. Normoxic perfusion of rat hearts at 28-32 °C was associated with inhibition of mitochondrial fission, evidenced by a reduced abundance of the active phosphorylated form of the fission receptor Drp1 (pDrp1). Abundance of the same residue was reduced in H9c2 cells subjected to hypothermic culture (25-32 °C), in addition to a reduced abundance of the Drp1 receptor MFF. Hypothermia-treated H9c2 cardiomyocytes exhibited elongated mitochondria and depressed rates of mitochondrial-associated oxygen consumption, which persisted upon rewarming. Hypothermia also promoted a reduction in mRNA expression of the capsaicin receptor TRPV1 in H9c2 cells. When normothermic H9c2 cells were transfected with TRPV1 siRNA we observed reduced pDrp1 and MFF abundance, elongated mitochondria, and reduced rates of mitochondrial-associated oxygen consumption, mimicking the effects of hypothermic culture. In conclusion hypothermia promoted elongation of cardiac mitochondria via reduced pDrp1 abundance which was also associated with suppression of cellular oxygen consumption. Silencing of TRPV1 in H9c2 cardiomyocytes reproduced the morphological and respirometric phenotype of hypothermia. This report demonstrates a novel mechanism of cold-induced inhibition of mitochondrial fission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cryobiol.2021.07.013DOI Listing
July 2021

The complete mitochondrial genome of Choroterpes (Euthralus) yixingensis (Ephemeroptera: Leptophlebiidae) and its mitochondrial protein-coding gene expression under imidacloprid stress.

Gene 2021 Oct 16;800:145833. Epub 2021 Jul 16.

College of Chemistry and Life Science, Zhejiang Normal University, Jinhua, Zhejiang Province, China; Key Lab of Wildlife Biotechnology, Conservation and Utilization of Zhejiang Province, Zhejiang Normal University, Jinhua, Zhejiang Province, China. Electronic address:

As one of the most common benthic invertebrates in freshwater, mayflies are very sensitive to changes in water quality and have high requirements for the water environment to allow their nymphs to successfully live and grow. Neonicotinoids, such as imidacloprid, can enter fresh water and pollute the aquatic environment. The present study had two goals: (1) investigate imidacloprid effects on mayfly larvae Choroterpes (Euthralus) yixingensis, and (2) contribute to the phylogenetic status of Ephemeroptera that has always been controversial. Nymphs were collected from Jinhua, China and exposed to different concentrations imidacloprid (5, 10, 20, and 40 μg/L) in the laboratory. Survival of C. yixingensis nymphs decreased as a function of time and imidacloprid concentration with only ~ 55% survival after 72 h exposure to 40 μg/L imidacloprid. After culture under 40 μg/L imidacloprid for 24 h, the steady state transcript levels of mitochondrial COX3, ND4 and ND4L genes were reduced to just 0.07 ± 0.11, 0.30 ± 0.16, and 0.28 ± 0.13 as compared with respective control values (P < 0.01). Steady state transcript levels of ND4 and ND4L were also significantly reduced in a dose-dependent manner (P < 0.05), suggesting that the steady state transcript pattern of these genes in mayfly nymphs can change in response to different levels of environmental contamination. Hence, the mitochondrial protein-coding genes of mayflies could potentially be developed as biomarkers for water ecotoxicity monitoring in the future. In addition, we used the mitochondrial genome sequence of C. yixingensis for an assessment of the phylogenetic tree of Ephemeroptera. The monophyly of Leptophlebiidae was supported and showed that Leptophlebiidae was a sister group to the clade (Baetidae + Caenidae).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2021.145833DOI Listing
October 2021

Stable suppression of skeletal muscle fructose-1,6-bisphosphatase during ground squirrel hibernation: Potential implications of reversible acetylation as a regulatory mechanism.

Cryobiology 2021 Jul 16. Epub 2021 Jul 16.

Institute of Biochemistry and Department of Chemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, K1S 5B6, Canada. Electronic address:

Mammalian hibernation is a period that involves substantial metabolic change in order to promote survival in harsh conditions, with animals typically relying on non-carbohydrate fuel stores during long bouts of torpor. However, the use and maintenance of carbohydrate fuel stores remains important during periods of arousal from torpor as well as when exiting hibernation. Gluconeogenesis plays a key role in maintaining glucose stores; however, little is known about this process within the muscles of hibernating mammals. Here, we used 13-lined ground squirrels (Ictidomys tridecemlineatus) as our model for mammalian hibernation, and showed that skeletal muscle fructose-1,6-bisphosphatase (FBPase; EC 3.1.3.11), the rate-limiting enzyme for the gluconeogenic pathway, was suppressed during torpor as compared to the euthermic control. A physical assessment of partially purified FBPase via exposure to increasing concentrations of the denaturant urea indicated that FBPase from the two conditions were structurally distinct. Western blot analysis suggests that the kinetic and physical differences between euthermic and torpid FBPase may be derived from differential acetylation, whereby increased acetylation of the torpid enzyme makes FBPase more rigid and less active. This study increases our understanding of skeletal muscle carbohydrate metabolism during mammalian hibernation and sets forth a potentially novel mechanism for the regulation of FBPase during environmental stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cryobiol.2021.07.006DOI Listing
July 2021

Oxidative stress concept updated: Definitions, classifications, and regulatory pathways implicated.

EXCLI J 2021 26;20:956-967. Epub 2021 May 26.

Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada.

Reactive oxygen species were discovered in living organisms in the early 1950's and their action has been implicated in diverse biological processes. First formulated by H. Sies in 1985[57], the oxidative stress concept stimulated substantial interest in reactive oxygen species and it is now common that fundamental research in various biomedical fields includes mention of research on the involvement of oxidative stress. Such strong interest has resulted in the development of definitions and classifications of oxidative stress and much research progress in the field. Although we clearly understand the limitations of various definitions or classifications, such parameters may help to provide quantitative descriptions, compare related processes among different laboratories, and introduce some measurable parameters. This paper highlights recent advances in the areas of oxidative stress definitions and the classification of oxidative stresses. Such items are directly associated with our understanding of the molecular mechanisms involved in organismal responses to oxidative insults. The knowledge accumulated to date indicates that selective expression of specific genes is a central player in the adaptive response to oxidative stress and reversible oxidation of cysteine residues of sensor proteins is a key process regulating responses to oxidative stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17179/excli2021-3596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278216PMC
May 2021

Increasing 28 mitogenomes of Ephemeroptera, Odonata and Plecoptera support the Chiastomyaria hypothesis with three different outgroup combinations.

PeerJ 2021 22;9:e11402. Epub 2021 Jun 22.

Key Lab of Wildlife Biotechnology, Conservation and Utilization of Zhejiang Province, Zhejiang Normal University, Jinhua, Zhejiang, China.

Background: The phylogenetic relationships of Odonata (dragonflies and damselflies) and Ephemeroptera (mayflies) remain unresolved. Different researchers have supported one of three hypotheses (Palaeoptera, Chiastomyaria or Metapterygota) based on data from different morphological characters and molecular markers, sometimes even re-assessing the same transcriptomes or mitochondrial genomes. The appropriate choice of outgroups and more taxon sampling is thought to eliminate artificial phylogenetic relationships and obtain an accurate phylogeny. Hence, in the current study, we sequenced 28 mt genomes from Ephemeroptera, Odonata and Plecoptera to further investigate phylogenetic relationships, the probability of each of the three hypotheses, and to examine mt gene arrangements in these species. We selected three different combinations of outgroups to analyze how outgroup choice affected the phylogenetic relationships of Odonata and Ephemeroptera.

Methods: Mitochondrial genomes from 28 species of mayflies, dragonflies, damselflies and stoneflies were sequenced. We used Bayesian inference (BI) and Maximum likelihood (ML) analyses for each dataset to reconstruct an accurate phylogeny of these winged insect orders. The effect of outgroup choice was assessed by separate analyses using three outgroups combinations: (a) four bristletails and three silverfish as outgroups, (b) five bristletails and three silverfish as outgroups, or (c) five diplurans as outgroups.

Results: Among these sequenced mitogenomes we found the gene arrangement in Heptageniidae (Ephemeroptera), and an inverted and translocated between the 12S RNA gene and the control region in Ephemerellidae (Ephemeroptera). The gene arrangement in Heptageniidae (Ephemeroptera) can be explained via the tandem-duplication and random loss model, and the transposition and inversion of genes in Ephemerellidae can be explained through the recombination and tandem duplication-random loss (TDRL) model. Our phylogenetic analysis strongly supported the Chiastomyaria hypothesis in three different outgroup combinations in BI analyses. The results also show that suitable outgroups are very important to determining phylogenetic relationships in the rapid evolution of insects especially among Ephemeroptera and Odonata. The mt genome is a suitable marker to investigate the phylogeny of inter-order and inter-family relationships of insects but outgroup choice is very important for deriving these relationships among winged insects. Hence, we must carefully choose the correct outgroup in order to discuss the relationships of Ephemeroptera and Odonata.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.11402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231340PMC
June 2021

Epigenetic regulation by DNA methyltransferases during torpor in the thirteen-lined ground squirrel Ictidomys tridecemlineatus.

Mol Cell Biochem 2021 Jun 30. Epub 2021 Jun 30.

Institute of Biochemistry and Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada.

The thirteen-lined ground squirrel, Ictidomys tridecemlineatus, is a mammal capable of lowering its T to almost 0 °C while undergoing deep torpor bouts over the winter. To decrease its metabolic rate to such a drastic extent, the squirrel must undergo multiple physiological, biological, and molecular alterations including downregulation of almost all nonessential processes. Epigenetic regulation allows for a dynamic range of transient phenotypes, allowing the squirrel to downregulate energy-expensive and nonessential pathways during torpor. DNA methylation is a prominent form of epigenetic regulation; therefore, the DNA methyltransferase (DNMT) family of enzymes were studied by measuring expression and activity levels of the five major proteins during torpor bouts. Additionally, specific cytosine marks on genomic DNA were quantified to further elucidate DNA methylation during hibernation. A tissue-specific response was observed that highlighted variant degrees of DNA methylation and DNMT expression/activity, demonstrating that DNA methylation is a highly complex form of epigenetic regulation and likely one of many regulatory mechanisms that enables metabolic rate depression in response to torpor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11010-021-04214-1DOI Listing
June 2021

Skeletal muscle of torpid Richardson's ground squirrels (Urocitellus richardsonii) exhibits a less active form of citrate synthase associated with lowered lysine succinylation.

Cryobiology 2021 Aug 26;101:28-37. Epub 2021 Jun 26.

Institute of Biochemistry and & Department of Biology, Carleton University, 1125 Colonel By, Drive, Ottawa Ontario, K1S 5B6, Canada. Electronic address:

Hibernation is a metabolic/physiological strategy employed by many mammals to cope with periods when energy usage is greater than its input. Animals undergoing hibernation need to greatly reduce their metabolic rate and reshape their catabolic processes to survive on stored triglycerides. Citrate synthase (CS) is one of only two irreversible steps in the citric acid cycle (CAC) and forms an important regulatory checkpoint that gates the entry of acetyl-CoA formed in glycolysis or fatty acid catabolism into this critical central metabolic hub. This study investigated the regulation of citrate synthase in the muscle tissue of a small mammalian hibernator through comparison of functional and structural properties. The results demonstrated a significant decrease in the V of purified torpid CS compared to the control euthermic enzyme (1.2-1.7 fold greater in the control) that was evident over a wide range of temperatures (8, 22 and 37 °C) that are encountered by the enzyme in hibernation. This was also reflected in the specific activity of the enzyme in crude muscle protein extracts. Analyzing the purified CS through immunoblotting demonstrated that the enzyme contained noticeably less lysine succinylation in the torpid state (about 50% of euthermic levels) and this was correlated with an increase in total levels of SIRT5, the enzyme responsible for mediating desuccinylation in the mitochondria (2.2 fold increase). Taken together, the results of this study support the idea that CS is inhibited during hibernation in the ground squirrel skeletal muscle and that this alteration could be mediated by decreases in succinylation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cryobiol.2021.06.006DOI Listing
August 2021

The first complete mitochondrial genome of (Okamoto, 1926) (Neuroptera: Myrmeleontidae) and its phylogeny.

Mitochondrial DNA B Resour 2021 Jun 14;6(7):1944-1946. Epub 2021 Jun 14.

College of Chemistry and Life Science, Zhejiang Normal University, Jinhua, Zhejiang Province, China.

The first complete mitochondrial genome of (Okamoto, 1926) was 15,797 bp in length, and contained 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, and the control region. Compared to the classic insect mitochondrial genome, showed a gene rearrangement of . The overall AT content of the mitochondrial genome was 75.5%. The monophyly of Ascalaphidae, Myrmeleontidae, Nemopteridae, Nymphidae, and Psychopsidae was supported in both BI and ML trees. And was a sister clade to the clade of genus .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/23802359.2021.1937362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205084PMC
June 2021

Novel tRNA gene rearrangements in the mitochondrial genomes of praying mantises (Mantodea: Mantidae): Translocation, duplication and pseudogenization.

Int J Biol Macromol 2021 Aug 22;185:403-411. Epub 2021 Jun 22.

College of Chemistry and Life Science, Zhejiang Normal University, Jinhua, Zhejiang Province, China; Key Lab of Wildlife Biotechnology, Conservation and Utilization of Zhejiang Province, Zhejiang Normal University, Jinhua, Zhejiang Province, China. Electronic address:

Gene rearrangements have been found in several mitochondrial genomes of Mantodea, located in the gene blocks CR-I-Q-M-ND2, COX1-K-D-ATP8 and ND3-A-R-N-S-E-F-ND5. We have sequenced one mitogenome of Amelidae (Yersinia mexicana) and six mitogenomes of Mantidae to discuss the mitochondrial gene rearrangement and the phylogenetic relationship within Mantidae. These mitogenomes showed rearrangements of tRNA genes except for Asiadodis yunnanensis and Hierodula zhangi. These novel gene rearrangements of Mantidae were primarily concentrated in the region of CR-I-Q-M-ND2, including gene translocation, duplication and pseudogenization. For the occurrences of these rearrangements, the tandem duplication-random loss (TDRL) model and slipped-strand mispairing model were suitable to explain. Large non-coding regions (LNCRs) located in the region of CR-I-Q-M-ND2 were detected in most Mantidae species, whereas some LNCRs had high similarity to the control region (CR). Both BI and ML phylogenetic analyses supported the monophyly of Mantidae and the paraphyly of Mantinae. The phylogenetic results with the gene order and the location of NCRs acted as forceful evidence that specific gene rearrangements and special LNCRs may be synapomorphies for several groups of mantises.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2021.06.096DOI Listing
August 2021

The first complete mitochondrial genome of (Gahan 1906) (Coleoptera: Cerambycidae: Cerambycinae) and its phylogeny.

Mitochondrial DNA B Resour 2021 Jun 7;6(7):1929-1931. Epub 2021 Jun 7.

College of Chemistry and Life Science, Zhejiang Normal University, Jinhua, PR China.

is a common species of Cerambycidae, reported from Vietnam, Nepal, Laos, Burma, and China. To date, no mitochondrial genomes of the genus have been reported. In this study, we sequenced and analyzed the first mitochondrial genome of to discuss its phylogenetic relationship within the subfamily Cerambycinae. This mitochondrial genome showed the typical insect gene arrangement: a circular molecule of 15,885 bp long with 13 protein-coding genes, two ribosomal RNA genes (rRNAs), and 22 transfer RNA genes (tRNAs). The AT content of the whole mitogenome was 74.2% with a high asymmetric nucleotide presentation revealed by a positive AT-skew (0.067) and a negative GC-skew (-0.178), whereas the AT content of the A + T rich region was 80%. The Maximum likelihood (ML) and Bayesian inference (BI) phylogenetic analyses showed that is a sister clade of
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/23802359.2021.1935354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189120PMC
June 2021

Factors that regulate expression patterns of insulin-like peptides and their association with physiological and metabolic traits in Drosophila.

Insect Biochem Mol Biol 2021 08 17;135:103609. Epub 2021 Jun 17.

Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, Ivano-Frankivsk, Ukraine; Research and Development University, Ivano-Frankivsk, Ukraine. Electronic address:

Insulin-like peptides (ILPs) and components of the insulin signaling pathway are conserved across different animal phyla. Eight ILPs (called DILPs) and two receptors, dInR and Lgr3, have been described in Drosophila. DILPs regulate varied physiological traits including lifespan, reproduction, development, feeding behavior, stress resistance and metabolism. At the same time, different conditions such as nutrition, dietary supplements and environmental factors affect the expression of DILPs. This review focuses primarily on DILP2, DILP3, and DILP5 which are produced by insulin-producing cells in the brain of Drosophila. Although they are produced by the same cells and can potentially compensate for each other, DILP2, DILP3, and DILP5 expression may be differentially regulated at the mRNA level. Thus, we summarized available data on the conditions affecting the expression profiles of these DILPs in adult Drosophila. The accumulated data indicate that transcript levels of DILPs are determined by (a) nutritional conditions such as the protein-to-carbohydrate ratio, (b) carbohydrate type within the diet, (c) malnutrition or complete starvation; (d) environmental factors such as stress or temperature; (e) mutations of single peptides that induce changes in the expression of the other peptides; and (f) dietary supplements of drugs or natural substances. Furthermore, manipulation of specific genes in a cell- and tissue-specific manner affects mRNA levels for DILPs and, thereby, modulates various physiological traits and metabolism in Drosophila.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ibmb.2021.103609DOI Listing
August 2021

Mitogenome Analysis of Four Lamiinae Species (Coleoptera: Cerambycidae) and Gene Expression Responses by When Infected with the Parasitic Nematode, .

Insects 2021 May 14;12(5). Epub 2021 May 14.

College of Chemistry and Life Science, Zhejiang Normal University, Jinhua 321004, China.

We determined the mitochondrial gene sequence of and three other mitogenomes of Lamiinae (Insect: Coleoptera: Cerambycidae) belonging to three genera (, and ) to enrich the mitochondrial genome database of Lamiinae and further explore the phylogenetic relationships within the subfamily. Phylogenetic trees of the Lamiinae were built using the Bayesian inference (BI) and maximum likelihood (ML) methods and the monophyly of , , and genera was supported. , and were closely related, suggesting they may also be potential vectors for the transmission of the pine wood pathogenic nematode () in addition to , a well-known vector of pine wilt disease. There is a special symbiotic relationship between and . As the native sympatric sibling species of , also has a specific relationship that is often overlooked. The analysis of mitochondrial gene expression aimed to explore the effect of on the energy metabolism of the respiratory chain of adults. Using RT-qPCR, we determined and analyzed the expression of eight mitochondrial protein-coding genes (, , , , , , , and ) between infected by and without the nematode. Expression of all the eight mitochondrial genes were up-regulated, particularly the and gene, which were up-regulated by 4-5-fold ( < 0.01). Since longicorn beetles have immune responses to nematodes, we believe that their relationship should not be viewed as symbiotic, but classed as parasitic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/insects12050453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157225PMC
May 2021

mTOR Signaling in Metabolic Stress Adaptation.

Biomolecules 2021 05 1;11(5). Epub 2021 May 1.

Institute of Biochemistry and Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, ON K1S 5B6, Canada.

The mechanistic target of rapamycin (mTOR) is a central regulator of cellular homeostasis that integrates environmental and nutrient signals to control cell growth and survival. Over the past two decades, extensive studies of mTOR have implicated the importance of this protein complex in regulating a broad range of metabolic functions, as well as its role in the progression of various human diseases. Recently, mTOR has emerged as a key signaling molecule in regulating animal entry into a hypometabolic state as a survival strategy in response to environmental stress. Here, we review current knowledge of the role that mTOR plays in contributing to natural hypometabolic states such as hibernation, estivation, hypoxia/anoxia tolerance, and dauer diapause. Studies across a diverse range of animal species reveal that mTOR exhibits unique regulatory patterns in an environmental stressor-dependent manner. We discuss how key signaling proteins within the mTOR signaling pathways are regulated in different animal models of stress, and describe how each of these regulations uniquely contribute to promoting animal survival in a hypometabolic state.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom11050681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147357PMC
May 2021

Mitochondria and the Frozen Frog.

Antioxidants (Basel) 2021 Apr 1;10(4). Epub 2021 Apr 1.

Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada.

The wood frog, , is the best-studied of a small group of amphibian species that survive whole body freezing during the winter months. These frogs endure the freezing of 65-70% of their total body water in extracellular ice masses. They have implemented multiple adaptations that manage ice formation, deal with freeze-induced ischemia/reperfusion stress, limit cell volume reduction with the production of small molecule cryoprotectants (glucose, urea) and adjust a wide variety of metabolic pathways for prolonged life in a frozen state. All organs, tissues, cells and intracellular organelles are affected by freeze/thaw and its consequences. This article explores mitochondria in the frozen frog with a focus on both the consequences of freezing (e.g., anoxia/ischemia, cell volume reduction) and mitigating defenses (e.g., antioxidants, chaperone proteins, upregulation of mitochondria-encoded genes, enzyme regulation, etc.) in order to identify adaptive strategies that defend and adapt mitochondria in animals that can be frozen for six months or more every year. A particular focus is placed on freeze-responsive genes in wood frogs that are encoded on the mitochondrial genome including , and RNA. These were strongly up-regulated during whole body freezing (24 h at -2.5 °C) in the liver and brain but showed opposing responses to two component stresses: strong upregulation in response to anoxia but no response to dehydration stress. This indicates that freeze-responsive upregulation of mitochondria-encoded genes is triggered by declining oxygen and likely has an adaptive function in supporting cellular energetics under indeterminate lengths of whole body freezing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox10040543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067143PMC
April 2021

Coordinated expression of Jumonji and AHCY under OCT transcription factor control to regulate gene methylation in wood frogs during anoxia.

Gene 2021 Jul 19;788:145671. Epub 2021 Apr 19.

Department of Biology, Carleton University, Ottawa K1S 5B6, Canada. Electronic address:

Wood frogs (Rana sylvatica) can survive extended periods of whole body freezing. Freezing imparts multiple stresses on cells that include anoxia and dehydration, but these can also be experienced as independent stresses. Under anoxia stress, energy metabolism is suppressed, and pro-survival pathways are prioritized to differentially regulate some transcription factors including OCT1 and OCT4. Jumonji C domain proteins (JMJD1A and JMJD2C) are hypoxia responsive demethylases whose expression is accelerated by OCT1 and OCT4 which act to demethylate genes related to the methionine cycle. The responses by these factors to 24 h anoxia exposure and 4 h aerobic recovery was analyzed in liver and skeletal muscle of wood frogs to assess their involvement in metabolic adaptation to oxygen limitation. Immunoblot results showed a decrease in JMJD1A levels under anoxia in liver and muscle, but an increase was observed in JMJD2C demethylase protein in anoxic skeletal muscle. Protein levels of adenosylhomocysteinase (AHCY) and methionine adenosyl transferase (MAT), enzymes of the methionine cycle, also showed an increase in the reoxygenated liver, whereas the levels decreased in muscle. A transcription factor ELISA showed a decrease in DNA binding by OCT1 in the reoxygenated liver and anoxic skeletal muscle, and transcript levels also showed tissue specific gene expression. The present study provides the first analysis of the role of the OCT1 transcription factor, associated proteins, and lysine demethylases in mediating responses to anoxia by wood frog tissues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2021.145671DOI Listing
July 2021

The Activation of Prosurvival Pathways in during Torpor.

Physiol Biochem Zool 2021 May-Jun;94(3):180-187

AbstractHibernation is a strategy used by some mammals to survive harsh winter conditions. Many small mammals, such as the little brown bat, , enter a long-term state of hibernation characterized by a period of deep torpor that can range from days to weeks. Torpid bats undergo metabolic rate depression that not only results in physiological changes but also promotes biochemical changes that favor survival. The present study utilizes multiplex technology to assess key early apoptosis markers and a select group of antioxidant enzymes in muscle, heart, and liver in euthermic controls and torpid bats. Muscle showed a significant decrease in the proapoptotic c-Jun N-terminal kinase and p53 and the antioxidant enzyme catalase but a significant increase in peroxiredoxin 2 levels. The heart responded similarly, with most proapoptotic proteins (caspase 8/9 and p53) remaining at low levels, while the antiapoptotic Bcl-2 protein significantly increased during torpor. There was no significant change in the antioxidant enzymes measured during torpor in the heart compared with the controls. The liver showed increases in catalase and Mn superoxide dismutase 2 enzymes during torpor, which correlated with activation of select antiapoptotic proteins and suppression of levels of proapoptotic ones. Overall, our data demonstrate that antiapoptotic and antioxidant defense responses have organ-specific regulation during torpor in bats. The induction of key antioxidant enzymes and antiapoptotic proteins may function as protective mechanisms that are necessary for surviving torpor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1086/714219DOI Listing
April 2021

Hypoxic Jumbo Squid Activate Neuronal Apoptosis but Not MAPK or Antioxidant Enzymes during Oxidative Stress.

Physiol Biochem Zool 2021 May-Jun;94(3):171-179

AbstractThe limitations that hypoxia imparts on mitochondrial oxygen supply are circumvented by the activation of anaerobic metabolism and prosurvival mechanisms in hypoxia-tolerant animals. To deal with the hypoxia that jumbo squid () experience in the ocean's depth, they depress their metabolic rate by up to 52% relative to normoxic conditions. This is coupled with molecular reorganization to facilitate their daily descents into the ocean's oxygen minimum zone, where they face not only low oxygen levels but also higher pressures and colder frigid waters. Our current study explores the tissue-specific hypoxia responses of three central processes: (1) antioxidant enzymes responsible for defending against oxidative stress, (2) early apoptotic machinery that signals the activation of cell death, and (3) mitogen-activated protein kinases (MAPKs) that act as central regulators of numerous cellular processes. Luminex xMAP technology was used to assess protein levels and phosphorylation states under normoxic and hypoxic conditions in brains, branchial hearts, and mantle muscles. Hypoxic brains were found to activate apoptosis via upregulation of phospho-p38, phospho-p53, activated caspase 8, and activated caspase 9, whereas branchial hearts were the only tissue to show an increase in antioxidant enzyme levels. Hypoxic muscles seemed the least affected by hypoxia. Our results suggest that hypoxic squid do not undergo large dynamic changes in the phosphorylation states of key apoptotic and central MAPK factors, except for brains, suggesting that these mechanisms are involved in squid hypometabolic responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1086/714097DOI Listing
April 2021

Middle aged turn point in parameters of oxidative stress and glucose catabolism in mouse cerebellum during lifespan: minor effects of every-other-day fasting.

Biogerontology 2021 06 30;22(3):315-328. Epub 2021 Mar 30.

Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko St., Ivano-Frankivsk, 76018, Ukraine.

The cerebellum is considered to develop aging markers more slowly than other parts of the brain. Intensification of free radical processes and compromised bioenergetics, critical hallmarks of normal brain aging, may be slowed down by caloric restriction. This study aimed to evaluate the intensity of oxidative stress and the enzymatic potential to utilize glucose via glycolysis or the pentose phosphate pathway (PPP) in the cerebellum of mice under ad libitum versus every-other-day fasting (EODF) feeding regimens. Levels of lipid peroxides, activities of antioxidant and key glycolytic and PPP enzymes were measured in young (6-month), middle-aged (12-month) and old (18-month) C57BL/6J mice. The cerebellum showed the most dramatic increase in lipid peroxide levels, antioxidant capacity and PPP key enzyme activities and the sharpest decline in the activities of key glycolytic enzymes under transition from young to middle age but these changes slowed when transiting from middle to old age. A decrease in the activity of the key glycolytic enzyme phosphofructokinase was accompanied by a concomitant increase in the activities of hexokinase and glucose-6-phosphate dehydrogenase (G6PDH), which may suggest that during normal cerebellar aging glucose metabolism shifts from glycolysis to the pentose phosphate pathway. The data indicate that intensification of free radical processes in the cerebellum occurred by middle age and that activation of the PPP together with increased antioxidant capacity can help to resist these changes into old age. However, the EODF regime did not significantly modulate or alleviate any of the metabolic processes studied in this analysis of the aging cerebellum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10522-021-09918-xDOI Listing
June 2021

Nrf2 activates antioxidant enzymes in the anoxia-tolerant red-eared slider turtle, Trachemys scripta elegans.

J Exp Zool A Ecol Integr Physiol 2021 04 26;335(4):426-435. Epub 2021 Mar 26.

Department of Biology, Institute of Biochemistry, Carleton University, Ottawa, Ontario, Canada.

The freshwater red-eared slider turtle, Trachemys scripta elegans, experiences weeks to months of anoxia at the bottom of ice-locked bodies of water in the winter. While this introduces anoxia-reoxygenation cycles similar to the ischemia-reperfusion events that mammals experience, T. s. elegans does not suffer any apparent tissue damage. To survive prolonged anoxia and prevent cellular damage associated with reactive oxygen species, these turtles have developed numerous adaptions, including highly effective antioxidant defenses. Herein, we examined the subcellular localization and protein expression of nuclear factor erythroid-2-related factor 2 (Nrf2), a central transcription factor responsible for modulating cellular antioxidant responses, that was found to be upregulated and localized to the nucleus in anoxic turtles. Additionally, we examined protein levels of glutathione S-transferases (GSTs) and manganese superoxide dismutase (MnSOD) antioxidant enzymes in anoxic liver, kidney, heart, and skeletal muscle tissues. MnSOD levels were significantly higher in heart and muscle during anoxia, and the four GST isozymes (GSTK1, GSTT1, GSTP1, and GSTM3) were elevated in a tissue-specific manner during anoxia and/or aerobic recovery. Together, these results indicate that Nrf2 is likely involved in activating downstream antioxidant genes in response to anoxic stress. These results provide a possible Nrf2-mediated transcriptional mechanism that supports existing findings of enhanced antioxidant defenses that allow T. s. elegans to cope with anoxia-reoxygenation cycles, and subsequent oxidative stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jez.2458DOI Listing
April 2021

Aspirin as a Potential Geroprotector: Experimental Data and Clinical Evidence.

Adv Exp Med Biol 2021 ;1286:145-161

Laboratory of Epigenetics, D.F. Chebotarev Institute of Gerontology, NAMS, Kyiv, Ukraine.

Aging is a biological process with effects at the molecular, cellular, tissue, organ, system, and organismal levels and is characterized by decline in physical function and higher risks of age-related diseases. The use of anti-aging drugs for disease prevention has become a high priority for science and is a new biomedicine trend. Geroprotectors are compounds which slow aging and increase lifespan of the organism in question. The common painkiller aspirin, a member of the non-steroidal anti-inflammatory drug (NSAID) family, is one of the potential geroprotective agents. Aspirin is often used in treatment of mild to moderate pain. It has anti-inflammatory and anti-pyretic properties and acts as an inhibitor of cyclooxygenase which results in inhibition of prostaglandin. Acetylsalicylic acid as an active compound of aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Aspirin has shown life-extending effects in numerous model organisms. This chapter reviews the evidence for clinical efficacy of aspirin including cardiovascular disease prevention, anti-cancer effects, and improvement of cognitive function. However, there are some limitations of these therapies, including the risk of excessive bleeding. We have also summarized numerous experimental and analytical data that support health and longevity benefits of aspirin treatment by affecting pro-longevity pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-3-030-55035-6_11DOI Listing
March 2021

Markers of tissue remodeling and inflammation in the white and brown adipose tissues of a model hibernator.

Cell Signal 2021 06 9;82:109975. Epub 2021 Mar 9.

Institute of Biochemistry, Departments of Biology and Chemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada. Electronic address:

The thirteen-lined ground squirrel is a model fat-storing hibernator that nearly doubles its weight in the fall to fuel metabolism with triglycerides throughout the winter months. Hibernator brown and white adipose tissue (BAT, WAT) are important to study in terms of their inflammatory profile and tissue remodeling mechanisms since controlled and natural regulation of these processes could inform new pharmacological interventions that limit oxidative stress and inflammation in the adipose tissues of humans suffering from obesity, promote non-shivering thermogenesis-mediated weight loss, or prevent tissue damage in transplantable organs emerging from cold-storage. Thus, markers of inflammation like cytokines and soluble receptors and tissue remodeling proteins such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) were investigated in normothermic, torpid, and arousing ground squirrels. Multiplex protein assays and western blotting revealed fewer changes in WAT compared to BAT. Pro-inflammatory IL-1α levels increased during torpor and soluble epidermal growth factor receptor protein levels increased during arousal in BAT. Given their known roles in other model systems, these proteins could regulate processes like adipogenesis, lipid catabolism, or cell motility. Decreased TIMP2 levels combined with maintained MMP2 or MMP3 protein levels suggested that BAT may avoid tissue remodeling until arousal. No changes in WAT inflammatory cytokines or soluble receptors as well as decreased MMP2 levels during torpor and arousal suggested inflammation and modification to the extracellular matrix is likely suppressed in WAT. This study emphasizes the fat-but-fit nature of the hibernating ground squirrel and the ability of its fat stores to suppress inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cellsig.2021.109975DOI Listing
June 2021
-->