290 results match your criteria diffusible reactive

Interaction of membrane-embedded cytochrome b-complexes with quinols: Classical Q-cycle and murburn model.

Cell Biochem Funct 2022 Jan 13. Epub 2022 Jan 13.

Karel de Grote University College, Antwerp University Association, Campus Hoboken, Hoboken, Belgium.

We recently proposed a diffusible reactive (oxygen) species (DRS/DROS) based function for cytochrome b complexes (CBC) and quinones (Q)/quinols (QH ) in the murburn model of bioenergetics. This proposal is in direct conflict with the classical purview of Q-cycle. Via extensive analyses of the structure-function correlations of membrane-quinones/quinols and proteins, we present qualitative and quantitative arguments to infer that the classical model cannot explain the energetics, kinetics, mechanism and probabilistic considerations. Read More

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January 2022

Murburn precepts for lactic-acidosis, Cori cycle, and Warburg effect: Interactive dynamics of dehydrogenases, protons, and oxygen.

J Cell Physiol 2021 Dec 20. Epub 2021 Dec 20.

Department of Biochemistry, Satyamjayatu: The Science & Ethics Foundation, Palakkad, Kerala, India.

It is unresolved why lactate is transported to the liver for further utilization within the physiological purview of Cori cycle, when muscles have more lactate dehydrogenase (LDH) than liver. We point out that the answer lies in thermodynamics/equilibriums. While the utilization of NADH for the reduction of pyruvate to lactate can be mediated via the classical mechanism, the oxidation of lactate (with/without the uphill reduction of NAD ) necessitates alternative physiological approaches. Read More

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December 2021

Why do cells need oxygen? Insights from mitochondrial composition and function.

Cell Biol Int 2021 Dec 17. Epub 2021 Dec 17.

Industrial Sciences and Technology, Karel de Grote-Hogeschool, Association University and High Schools Antwerp, Antwerpen, Belgium.

Mitochondrial membrane-embedded redox proteins are classically perceived as deterministic "electron transport chain" (ETC) arrays cum proton pumps; and oxygen is seen as an "immobile terminal electron acceptor." This is untenable because: (1) there are little free protons to be pumped out of the matrix; (2) proton pumping would be highly endergonic; (3) ETC-chemiosmosis-rotary ATP synthesis proposal is "irreducibly complex"/"non-evolvable" and does not fit with mitochondrial architecture or structural/distribution data of the concerned proteins/components; (4) a plethora of experimental observations do not conform to the postulates/requisites; for example, there is little evidence for viable proton-pumps/pH-gradient in mitochondria, trans-membrane potential (TMP) is non-fluctuating/non-trappable, oxygen is seen to give copious "diffusible reactive (oxygen) species" (DRS/DROS) in milieu, etc. Quite contrarily, the newly proposed murburn model's tenets agree with known principles of energetics/kinetics, and builds on established structural data and reported observations. Read More

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December 2021

Quantification of intracellular HNO delivery with capillary zone electrophoresis.

Nitric Oxide 2022 Jan 27;118:49-58. Epub 2021 Oct 27.

Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721, USA; BIO5 Institute, University of Arizona, Tucson, AZ, 85721, USA. Electronic address:

Redox signaling, wherein reactive and diffusible small molecules are channeled into specific messenger functions, is a critical component of signal transduction. A central principle of redox signaling is that the redox modulators are produced in a highly controlled fashion to specifically modify biotargets. Thiols serve as primary mediators of redox signaling as a function of the rich variety of adducts, which allows initiation of distinct cellular effects. Read More

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January 2022

Peroxiredoxins as Potential Targets for Cardiovascular Disease.

Antioxidants (Basel) 2021 Aug 3;10(8). Epub 2021 Aug 3.

Department of Life Sciences, Heart-Immune-Brain Network Research Center, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Korea.

Increased oxidative stress (OS) is considered a common etiology in the pathogenesis of cardiovascular disease (CVD). Therefore, the precise regulation of reactive oxygen species (ROS) in cardiovascular cells is essential to maintain normal physiological functions. Numerous regulators of cellular homeostasis are reportedly influenced by ROS. Read More

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Validating the predictions of murburn model for oxygenic photosynthesis: Analyses of ligand-binding to protein complexes and cross-system comparisons.

J Biomol Struct Dyn 2021 Jul 30:1-33. Epub 2021 Jul 30.

RedOx Lab, Department of Life Sciences, Satyamjayatu: The Science & Ethics Foundation, Palakkad District, Kerala, India.

In this second half of our treatise on oxygenic photosynthesis, we provide support for the murburn model of the light reaction of photosynthesis and ratify key predictions made in the first part. Molecular docking and visualization of various ligands of quinones/quinols (and their derivatives) with PS II/Cytochrome complexes did not support chartered 2e-transport role of quinols. A broad variety of herbicides did not show any affinity/binding-based rationales for inhibition of photosynthesis. Read More

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Structure-function correlations and system dynamics in oxygenic photosynthesis: classical perspectives and murburn precepts.

J Biomol Struct Dyn 2021 Jul 29:1-27. Epub 2021 Jul 29.

Satyamjayatu: The Science & Ethics Foundation, Kulappully, Kerala, India.

Highlights: Contemporary beliefs on oxygenic photosynthesis are critiqued.Murburn model is suggested as an alternative explanation.In the new model, diffusible reactive species are the main protagonists. Read More

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MICAL1 regulates actin cytoskeleton organization, directional cell migration and the growth of human breast cancer cells as orthotopic xenograft tumours.

Cancer Lett 2021 10 24;519:226-236. Epub 2021 Jul 24.

Department of Chemistry and Biology, Ryerson University, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Electronic address:

The Molecule Interacting with CasL 1 (MICAL1) monooxygenase has emerged as an important regulator of cytoskeleton organization via actin oxidation. Although filamentous actin (F-actin) increases MICAL1 monooxygenase activity, hydrogen peroxide (HO) is also generated in the absence of F-actin, suggesting that diffusible HO might have additional functions. MICAL1 gene disruption by CRISPR/Cas9 in MDA MB 231 human breast cancer cells knocked out (KO) protein expression, which affected F-actin organization, cell size and motility. Read More

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October 2021

Rubrolone production by Dactylosporangium vinaceum: biosynthesis, modulation and possible biological function.

Appl Microbiol Biotechnol 2021 Jul 30;105(13):5541-5551. Epub 2021 Jun 30.

Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France.

Rare actinomycetes are likely treasure troves for bioactive natural products, and it is therefore important that we enrich our understanding of biosynthetic potential of these relatively understudied bacteria. Dactylosporangium are a genus of such rare Actinobacteria that are known to produce a number of important antibacterial compounds, but for which there are still no fully assembled reference genomes, and where the extent of encoded biosynthetic capacity is not defined. Dactylosporangium vinaceum (NRRL B-16297) is known to readily produce a deep wine red-coloured diffusible pigment of unknown origin, and it was decided to define the chemical identity of this natural product pigment, and in parallel use whole genome sequencing and transcriptional analysis to lay a foundation for understanding the biosynthetic capacity of these bacteria. Read More

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Mediated Electrochemical Probing: A Systems-Level Tool for Redox Biology.

ACS Chem Biol 2021 07 22;16(7):1099-1110. Epub 2021 Jun 22.

Institute for Bioscience & Biotechnology Research, University of Maryland, College Park, Maryland 20742, United States.

Biology uses well-known redox mechanisms for energy harvesting (e.g., respiration), biosynthesis, and immune defense (e. Read More

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Helminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis.

Sci Rep 2021 06 16;11(1):12718. Epub 2021 Jun 16.

Department of Biomedical Sciences, The University of North Dakota School of Medicine and Health Sciences, 1301 N Columbia Road, Grand Forks, ND, 58202-9037, USA.

Despite their protective antimicrobial function, neutrophil extracellular traps (NETs) have been implicated in propagation of inflammatory responses in several disease conditions including sepsis. Highly diffusible exogenous ROS produced under such inflammatory conditions, can induce exuberant NETs, thus making inhibition of NETs desirable in inflammatory diseases. Here we report that helminth parasite excretory/secretory factors termed as parasitic ligands (PL) inhibit ROS-induced NETs by blocking the activation of nonselective calcium permeable channel Transient Receptor Potential Melastatin 2 (TRPM2). Read More

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The murburn precepts for aerobic respiration and redox homeostasis.

Prog Biophys Mol Biol 2021 Dec 10;167:104-120. Epub 2021 Jun 10.

Institute of Chemical Kinetics and Combustion, Russian Academy of Sciences, St. Institutskaya 3, 630090, Novosibirsk, Russia. Electronic address:

Murburn concept is a new perspective to metabolism which posits that certain redox enzymes/proteins mediate catalysis outside their active site, via diffusible reactive oxygen species (DROS, usually deemed as toxic wastes). We have recently questioned the proton-centric chemiosmotic rotary ATP synthesis (CRAS) explanation for mitochondrial oxidative phosphorylation (mOxPhos) and proposed an oxygen-centric murburn model in lieu. Herein, the chemical equations and thermodynamic foundations for this new model of mOxPhos are detailed. Read More

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December 2021

Effect of Media with Different Glycerol Concentrations on Sheep Red Blood Cells' Viability In Vitro.

Animals (Basel) 2021 May 28;11(6). Epub 2021 May 28.

Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy.

The use of high doses of glycerol as a livestock feed supplement is followed by a rapid increase in plasma concentrations and consequently in plasma osmolality. Moreover, glycerol is a highly diffusible molecule that can readily permeate the red blood cell (RBC) membrane following a concentration gradient. A rise in glycerol plasma concentrations can thus alter RBC homeostasis. Read More

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Mechanism of electron transfers mediated by cytochromes and in mitochondria and endoplasmic reticulum: classical and murburn perspectives.

J Biomol Struct Dyn 2021 May 17:1-18. Epub 2021 May 17.

Satyamjayatu: The Science & Ethics Foundation, Palakkad District, Kerala State, India.

We explore the mechanism of electron transfers mediated by cytochrome , a soluble protein involved in mitochondrial oxidative phosphorylation and cytochrome , a microsomal membrane protein acting as a redox aide in xenobiotic metabolism. We found minimal conservation in the sequence and surface amino acid residues of cytochrome proteins among divergent species. Therefore, we question the evolutionary logic for electron transfer (ET) occurring through affinity binding via recognition of specific surface residues/topography. Read More

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Hemoglobin catalyzes ATP-synthesis in human erythrocytes: a murburn model.

J Biomol Struct Dyn 2021 May 17:1-13. Epub 2021 May 17.

Satyamjayatu: The Science & Ethics Foundation, Kulappully, India.

Blood hemoglobin (Hb), known to transport oxygen, is the most abundant globular protein in humans. Erythrocytes have ∼10 M concentration of ATP in steady-state and we estimate that this high amounts cannot be formed from 10 - 10 M levels of precursors via substrate-level phosphorylation of glycolysis. To account for this discrepancy, we propose that Hb serves as a 'murzyme' (a redox enzyme working along the principles of murburn concept), catalyzing the synthesis of the major amounts of ATP found in erythrocytes. Read More

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Interplay of two transcription factors for recruitment of the chromatin remodeling complex modulates fungal nitrosative stress response.

Nat Commun 2021 05 6;12(1):2576. Epub 2021 May 6.

State Key Laboratory of Rice Biology, Zhejiang University, Hangzhou, China.

Nitric oxide (NO) is a diffusible signaling molecule that modulates animal and plant immune responses. In addition, reactive nitrogen species derived from NO can display antimicrobial activities by reacting with microbial cellular components, leading to nitrosative stress (NS) in pathogens. Here, we identify FgAreB as a regulator of the NS response in Fusarium graminearum, a fungal pathogen of cereal crops. Read More

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J Zoo Wildl Med 2021 Apr;52(1):406-412

Zoological Health Program, Wildlife Conservation Society, Bronx, New York City, NY 10460, USA.

This study describes the novel use of diffusible iodine-based contrast-enhanced computed tomography (diceCT) as a digital necropsy aid. DiceCT was used postmortem to evaluate the cause of progressive respiratory disease in a juvenile maleo (). The technique facilitated soft-tissue contrast and a three-dimensional investigation of sinus and choanal anatomy as a means to identify normal and pathologic morphologies. Read More

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A tandem activity-based sensing and labeling strategy enables imaging of transcellular hydrogen peroxide signaling.

Proc Natl Acad Sci U S A 2021 03;118(9)

Department of Chemistry, University of California, Berkeley, CA 94720;

Reactive oxygen species (ROS) like hydrogen peroxide (HO) are transient species that have broad actions in signaling and stress, but spatioanatomical understanding of their biology remains insufficient. Here, we report a tandem activity-based sensing and labeling strategy for HO imaging that enables capture and permanent recording of localized HO fluxes. Peroxy Green-1 Fluoromethyl (PG1-FM) is a diffusible small-molecule probe that senses HO by a boronate oxidation reaction to trigger dual release and covalent labeling of a fluorescent product, thus preserving spatial information on local HO changes. Read More

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MicroRNA-140 silencing represses the incidence of Alzheimer's disease.

Neurosci Lett 2021 07 30;758:135674. Epub 2021 Jan 30.

The First Department of Neurology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161000, PR China.

Alzheimer's disease (AD) is a neurodegenerative condition leading to severe disability from progressive impairments in cognitive functions including memory and learning. Non-coding microRNAs (miRNAs or miRs) have been linked to the pathogenesis of AD. The present study aimed to investigate the clinical significance and biological function of miR-140 in AD. Read More

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Murburn Precepts for Cytochrome P450 Mediated Drug/Xenobiotic Metabolism and Homeostasis.

Curr Drug Metab 2021 ;22(4):315-326

Satyamjayatu: The Science & Ethics Foundation, Snehatheeram, Kulappully, Shoranur-2 (PO), Kerala-679122, India.

Aims: We aim to demonstrate why deeming diffusible reactive oxygen species (DROS) as toxic wastes do not afford a comprehensive understanding of cytochrome P450 mediated microsomal xenobiotic metabolism (mXM).

Background: Current pharmacokinetic investigations consider reactive oxygen species formed in microsomal reactions as toxic waste products, whereas our works (Manoj et al., 2016) showed that DROS are the reaction mainstay in cytochrome P450 mediated metabolism and that they play significant roles in explaining several unexplained physiologies. Read More

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December 2021

Oxygen sensing, mitochondrial biology and experimental therapeutics for pulmonary hypertension and cancer.

Free Radic Biol Med 2021 07 12;170:150-178. Epub 2021 Jan 12.

Department of Medicine, Queen's University, 94 Stuart St., Kingston, Ontario, K7L 3N6, Canada. Electronic address:

The homeostatic oxygen sensing system (HOSS) optimizes systemic oxygen delivery. Specialized tissues utilize a conserved mitochondrial sensor, often involving NDUFS2 in complex I of the mitochondrial electron transport chain, as a site of pO-responsive production of reactive oxygen species (ROS). These ROS are converted to a diffusible signaling molecule, hydrogen peroxide (HO), by superoxide dismutase (SOD2). Read More

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Deciphering molecular interactions by proximity labeling.

Nat Methods 2021 02 11;18(2):133-143. Epub 2021 Jan 11.

Department of Genetics, Stanford University, Stanford, CA, USA.

Many biological processes are executed and regulated through the molecular interactions of proteins and nucleic acids. Proximity labeling (PL) is a technology for tagging the endogenous interaction partners of specific protein 'baits', via genetic fusion to promiscuous enzymes that catalyze the generation of diffusible reactive species in living cells. Tagged molecules that interact with baits can then be enriched and identified by mass spectrometry or nucleic acid sequencing. Read More

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February 2021

Inflaming the Brain with Iron.

Antioxidants (Basel) 2021 Jan 6;10(1). Epub 2021 Jan 6.

Department of Biology, Faculty of Sciences, Universidad de Chile, 7800024 Santiago, Chile.

Iron accumulation and neuroinflammation are pathological conditions found in several neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Iron and inflammation are intertwined in a bidirectional relationship, where iron modifies the inflammatory phenotype of microglia and infiltrating macrophages, and in turn, these cells secrete diffusible mediators that reshape neuronal iron homeostasis and regulate iron entry into the brain. Secreted inflammatory mediators include cytokines and reactive oxygen/nitrogen species (ROS/RNS), notably hepcidin and nitric oxide (·NO). Read More

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January 2021

Inhibition of Myeloperoxidase.

Handb Exp Pharmacol 2021 ;264:261-285

Department of Chemistry, Institute of Biochemistry, University of Natural Resources and Life Sciences, Vienna, Austria.

Myeloperoxidase participates in innate immune defense mechanism through formation of microbicidal reactive oxidants and diffusible radical species. A unique activity is its ability to use chloride as a cosubstrate with hydrogen peroxide to generate chlorinating oxidants such as hypochlorous acid, a potent antimicrobial agent. However, chronic MPO activation can lead to indiscriminate protein modification causing tissue damage, and has been associated with chronic inflammatory diseases, atherosclerosis, and acute cardiovascular events. Read More

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February 2021

DJ-1 Proteoforms in Breast Cancer Cells: The Escape of Metabolic Epigenetic Misregulation.

Cells 2020 08 26;9(9). Epub 2020 Aug 26.

Laboratory of Proteomics, Research Center on Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, Magna Græcia Universityof Catanzaro, S Venuta University Campus, 88100 Catanzaro, Italy.

Enhanced glycolysis is a hallmark of breast cancer. In cancer cells, the high glycolytic flux induces carbonyl stress, a damaging condition in which the increase of reactive carbonyl species makes DNA, proteins, and lipids more susceptible to glycation. Together with glucose, methylglyoxal (MGO), a byproduct of glycolysis, is considered the main glycating agent. Read More

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Cross-Talk between NADPH Oxidase and Mitochondria: Role in ROS Signaling and Angiogenesis.

Cells 2020 08 6;9(8). Epub 2020 Aug 6.

Vascular Biology Center, Departments of Pharmacology and Toxicology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA.

Angiogenesis, a new vessel formation from the pre-existing ones, is essential for embryonic development, wound repair and treatment of ischemic heart and limb diseases. However, dysregulated angiogenesis contributes to various pathologies such as diabetic retinopathy, atherosclerosis and cancer. Reactive oxygen species (ROS) derived from NADPH oxidase (NOX) as well as mitochondria play an important role in promoting the angiogenic switch from quiescent endothelial cells (ECs). Read More

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Hyperphosphorylation Renders Tau Prone to Aggregate and to Cause Cell Death.

Mol Neurobiol 2020 Nov 11;57(11):4704-4719. Epub 2020 Aug 11.

Department of Biochemistry and Molecular Biology, Michigan State University, 603 Wilson Road, Room 401, East Lansing, MI, 48824, USA.

Alzheimer's disease (AD) is a neurodegenerative disorder without a cure or prevention to date. Hyperphosphorylated tau forms the neurofibrillary tangles (NFTs) that correlate well with the progression of cognitive impairments. Animal studies demonstrated the pathogenic role of hyperphosphorylated tau. Read More

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November 2020

Oxidants in Physiological Processes.

Ulla G Knaus

Handb Exp Pharmacol 2021 ;264:27-47

Conway Institute, School of Medicine, University College Dublin, Dublin, Ireland.

A number of diseases and conditions have been associated with prolonged or persistent exposure to non-physiological levels of reactive oxygen species (ROS). Similarly, ROS underproduction due to loss-of-function mutations in superoxide or hydrogen peroxide (HO)-generating enzymes is a risk factor or causative for certain diseases. However, ROS are required for basic cell functions; in particular the diffusible second messenger HO that serves as signaling molecule in redox processes. Read More

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February 2021

Tau Protein as a New Regulator of Cellular Prion Protein Transcription.

Mol Neurobiol 2020 Oct 18;57(10):4170-4186. Epub 2020 Jul 18.

Molecular and Cellular Neurobiotechnology, Institute for Bioengineering of Catalonia (IBEC), Scientific Park of Barcelona, The Barcelona Institute for Science and Technology (BIST), Baldiri and Reixac 15-21, 08028, Barcelona, Spain.

Cellular prion protein (PrP) is largely responsible for transmissible spongiform encephalopathies (TSEs) when it becomes the abnormally processed and protease resistant form PrP. Physiological functions of PrP include protective roles against oxidative stress and excitotoxicity. Relevantly, PrP downregulates tau levels, whose accumulation and modification are a hallmark in the advance of Alzheimer's disease (AD). Read More

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October 2020

Excess hydrogen peroxide inhibits head and foot regeneration in hydra by affecting DNA repair and expression of essential genes.

J Biochem Mol Toxicol 2020 Nov 6;34(11):e22577. Epub 2020 Jul 6.

Department of Zoology, Savitribai Phule Pune University, Pune, India.

Reactive oxygen species (ROS) are necessary for various cellular processes. However, excess ROS cause damage to many biological molecules and therefore must be tightly regulated in time and space. Hydrogen peroxide (H O ) is the most commonly used ROS as second messenger in the cell. Read More

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November 2020