46,120 results match your criteria heme metabolism


Bilirubin: the yellow hormone?

J Hepatol 2021 Jun 18. Epub 2021 Jun 18.

Fondazione Italiana Fegato, Trieste, Italy. Electronic address:

Bilirubin is a tetrapyrrolic compound originating from heme catabolism. Although originally considered only a waste product, potentially dangerous for human health, it becomes now increasingly evident that this molecule represents an important modulator of various biological functions in the human body. Bilirubin appears to have versatile functions, from cell signaling (behaving almost as a ¨real¨ hormonal substance), modulation of metabolism, to immune system affecting biological activities with apparent clinical and even therapeutic consequences. Read More

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Functional assessment of the effects of CYP3A4 variants on acalabrutinib metabolism in vitro.

Chem Biol Interact 2021 Jun 18:109559. Epub 2021 Jun 18.

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, PR China. Electronic address:

Aim: We aimed (i) to study the effects of genetic polymorphism of cytochrome P450 3A4 (CYP3A4) and drug interactions on acalabrutinib (ACA) metabolism and (ii) to investigate the mechanisms underlying the effects of CYP3A4 variants on the differential kinetic profiles of ACA and ibrutinib.

Method: Recombinant human CYP3A4 and variants were expressed using a Bac-to-Bac baculovirus expression system. The cell microsome was prepared and subjected to kinetic study. Read More

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VHL regulates the sensitivity of clear cell renal cell carcinoma to SIRT4-mediated metabolic stress via HIF-1α/HO-1 pathway.

Cell Death Dis 2021 Jun 16;12(7):621. Epub 2021 Jun 16.

Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.

Clear cell renal cell carcinomas (ccRCC) reprogram carbon metabolism responses to hypoxia, thereby promoting utilization of glutamine. Recently, sirtuin 4 (SIRT4), a novel molecular has turned out to be related to alternating glutamine metabolism and modulating the tumor microenvironment. However, the role of SIRT4 in ccRCC remains poorly understood. Read More

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The heme synthesis-export system regulates the tricarboxylic acid cycle flux and oxidative phosphorylation.

Cell Rep 2021 Jun;35(11):109252

Molecular Biotechnology Center (MBC), Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy. Electronic address:

Heme is an iron-containing porphyrin of vital importance for cell energetic metabolism. High rates of heme synthesis are commonly observed in proliferating cells. Moreover, the cell-surface heme exporter feline leukemia virus subgroup C receptor 1a (FLVCR1a) is overexpressed in several tumor types. Read More

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Influence of Consumption of Orange Juice (Citrus Sinensis) on Cardiac Remodeling of Rats Submitted to Myocardial Infarction.

Arq Bras Cardiol 2021 Jun;116(6):1127-1136

Universidade Estadual Paulista Júlio de Mesquita Filho Campus de Botucatu - Faculdade de Medicina de Botucatu , Botucatu , SP - Brasil.

Background: Orange juice (OJ) is rich in polyphenols with anti-inflammatory and antioxidant properties. After myocardial infarction (MI), complex changes occur in cardiac structure and function, which is known as cardiac remodeling (CR). Oxidative stress and inflammation can modulate this process. Read More

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Pathways of iron and sulfur acquisition, cofactor assembly, destination, and storage in diverse archaeal methanogens, methanotrophs, and alkanotrophs.

J Bacteriol 2021 Jun 14:JB0011721. Epub 2021 Jun 14.

Department of Microbiology and Immunology, Montana State University, Bozeman, Montana 59717.

Archaeal methanogens, methanotrophs, and alkanotrophs have a high demand for iron (Fe) and sulfur (S); however, little is known of how they acquire, traffic, deploy, and store these elements. Here, we examined the distribution of homologs of proteins mediating key steps in Fe/S metabolism in model microorganisms, including iron(II) sensing/uptake (FeoAB), sulfide extraction from cysteine (SufS), the biosynthesis of iron-sulfur [Fe-S] clusters (SufBCDE), siroheme (Pch2-dehydrogenase), protoheme (AhbABCD), and cytochrome (CcmCF), and iron-storage/detoxification (Bfr, FtrA, IssA), among 326 publicly available, complete or metagenome-assembled genomes of archaeal methanogens/methanotrophs/alkanotrophs. Results indicate several prevalent but non-universal features including FeoB, SufBC, and the biosynthetic apparatus for the basic tetrapyrrole scaffold as well as its siroheme (and F) derivatives. Read More

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Cholesterol Metabolic Reprogramming in Cancer and Its Pharmacological Modulation as Therapeutic Strategy.

Front Oncol 2021 24;11:682911. Epub 2021 May 24.

Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.

Cholesterol is a ubiquitous sterol with many biological functions, which are crucial for proper cellular signaling and physiology. Indeed, cholesterol is essential in maintaining membrane physical properties, while its metabolism is involved in bile acid production and steroid hormone biosynthesis. Additionally, isoprenoids metabolites of the mevalonate pathway support protein-prenylation and dolichol, ubiquinone and the heme biosynthesis. Read More

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Dihydroartemisinin overcomes the resistance to osimertinib in EGFR-mutant non-small-cell lung cancer.

Pharmacol Res 2021 Jun 1;170:105701. Epub 2021 Jun 1.

Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China; College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Rd, Nanjing 210023, China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address:

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), is commonly used to treat EGFR-mutant non-small-cell lung cancer (NSCLC). However, acquired resistance to mutant EGFR (T790M) can evolve following osimertinib treatment. High reactive oxygen species (ROS) levels in lung cancer cells can influence heme levels and have an impact on osimertinib resistance. Read More

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Carbon monoxide exposure activates ULK1 via AMPK phosphorylation in murine embryonic fibroblasts.

Int J Vitam Nutr Res 2021 Jun 2:1-10. Epub 2021 Jun 2.

Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

Carbon monoxide (CO) is endogenously produced upon degradation of heme by heme oxygenases (HOs) and is suggested to act as a gaseous signaling molecule. The expression of HO-1 is triggered by the Nrf2-Keap1 signaling pathway which responds to exogenous stress signals and dietary constituents such as flavonoids and glucosinolates or reactive metabolic intermediates like 4-hydroxynonenal. Endogenous CO affects energy metabolism, regulates the utilization of glucose and addresses CYP450 enzymes. Read More

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Significance of Heme and Heme Degradation in the Pathogenesis of Acute Lung and Inflammatory Disorders.

Authors:
Stefan W Ryter

Int J Mol Sci 2021 May 24;22(11). Epub 2021 May 24.

Proterris, Inc., Boston, MA 02118, USA.

The heme molecule serves as an essential prosthetic group for oxygen transport and storage proteins, as well for cellular metabolic enzyme activities, including those involved in mitochondrial respiration, xenobiotic metabolism, and antioxidant responses. Dysfunction in both heme synthesis and degradation pathways can promote human disease. Heme is a pro-oxidant via iron catalysis that can induce cytotoxicity and injury to the vascular endothelium. Read More

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Erythrocytes: Central Actors in Multiple Scenes of Atherosclerosis.

Int J Mol Sci 2021 May 29;22(11). Epub 2021 May 29.

Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), INSERM, UMR 1188, Université de La Réunion, 97400 Saint Denis, France.

The development and progression of atherosclerosis (ATH) involves lipid accumulation, oxidative stress and both vascular and blood cell dysfunction. Erythrocytes, the main circulating cells in the body, exert determinant roles in the gas transport between tissues. Erythrocytes have long been considered as simple bystanders in cardiovascular diseases, including ATH. Read More

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Structural Basis for the Diminished Ligand Binding and Catalytic Ability of Human Fetal-Specific CYP3A7.

Int J Mol Sci 2021 May 29;22(11). Epub 2021 May 29.

Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697-3900, USA.

Cytochrome P450 3A7 (CYP3A7) is a fetal/neonatal liver enzyme that participates in estriol synthesis, clearance of all-trans retinoic acid, and xenobiotic metabolism. Compared to the closely related major drug-metabolizing enzyme in adult liver, CYP3A4, the ligand binding and catalytic capacity of CYP3A7 are substantially reduced. To better understand the structural basis for these functional differences, the 2. Read More

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Characterization of the CYP3A4 Enzyme Inhibition Potential of Selected Flavonoids.

Molecules 2021 May 19;26(10). Epub 2021 May 19.

Faculty of Medicine, University of Mostar, Zrinskog Frankopana 34, 88000 Mostar, Bosnia and Herzegovina.

Acacetin, apigenin, chrysin, and pinocembrin are flavonoid aglycones found in foods such as parsley, honey, celery, and chamomile tea. Flavonoids can act as substrates and inhibitors of the CYP3A4 enzyme, a heme containing enzyme responsible for the metabolism of one third of drugs on the market. The aim of this study was to investigate the inhibitory effect of selected flavonoids on the CYP3A4 enzyme, the kinetics of inhibition, the possible covalent binding of the inhibitor to the enzyme, and whether flavonoids can act as pseudo-irreversible inhibitors. Read More

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Activation of Nrf2/HO-1 by Peptide YD1 Attenuates Inflammatory Symptoms through Suppression of TLR4/MYyD88/NF-κB Signaling Cascade.

Int J Mol Sci 2021 May 13;22(10). Epub 2021 May 13.

Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju 501-759, Korea.

In this study, we investigate the immunomodulatory effects of a novel antimicrobial peptide, YD1, isolated from Kimchi, in both in vitro and in vivo models. We establish that YD1 exerts its anti-inflammatory effects via up-regulation of the Nrf2 pathway, resulting in the production of HO-1, which suppresses activation of the NF-κB pathway, including the subsequent proinflammatory cytokines IL-1β, IL-6, and TNF-α. We also found that YD1 robustly suppresses nitric oxide (NO) and prostaglandin E2 (PGE) production by down-regulating the expression of the upstream genes, iNOS and COX-2, acting as a strong antioxidant. Read More

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Identification of Binding Regions of Bilirubin in the Ligand-Binding Pocket of the Peroxisome Proliferator-Activated Receptor-A (PPARalpha).

Molecules 2021 May 17;26(10). Epub 2021 May 17.

Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, 760 Press Avenue, Healthy Kentucky Research Building, Lexington, KY 40508, USA.

Recent work has shown that bilirubin has a hormonal function by binding to the peroxisome proliferator-activated receptor-α (PPARα), a nuclear receptor that drives the transcription of genes to control adiposity. Our previous in silico work predicted three potential amino acids that bilirubin may interact with by hydrogen bonding in the PPARα ligand-binding domain (LBD), which could be responsible for the ligand-induced function. To further reveal the amino acids that bilirubin interacts with in the PPARα LBD, we harnessed bilirubin's known fluorescent properties when bound to proteins such as albumin. Read More

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Neuroprotective Effects and Mechanisms of Procyanidins In Vitro and In Vivo.

Molecules 2021 May 17;26(10). Epub 2021 May 17.

Department of Food Science and Nutrition, Zhejiang University, Hangzhou 310000, China.

This study evaluated the neuroprotective effects and mechanisms of procyanidins (PCs). In vitro, rat pheochromocytoma cells (PC12 cells) were exposed to PCs (1, 2 or 4 μg/mL) or N-Acetyl-L-cysteine (NAC) (20 μM) for 24 h, and then incubated with 200 μM of HO for 24 h. Compared with HO alone, PCs significantly increased antioxidant activities (e. Read More

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5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease.

Biomedicines 2021 May 20;9(5). Epub 2021 May 20.

Intract Pharma Limited, London Bioscience Innovation Centre, London NW1 0NH, UK.

5-Aminolevulinic acid (5-ALA) is a naturally occurring nonprotein amino acid licensed as an optical imaging agent for the treatment of gliomas. In recent years, 5-ALA has been shown to possess anti-inflammatory and immunoregulatory properties through upregulation of heme oxygenase-1 via enhancement of porphyrin, indicating that it may be beneficial for the treatment of inflammatory conditions. This study systematically examines 5-ALA for use in inflammatory bowel disease (IBD). Read More

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Implication of a Key Region of Six Genes Involved in Siroheme Synthesis, Nitrite Reductase Production and Iron Cluster Repair in the Bacterial Response to Nitric Oxide Stress.

Int J Mol Sci 2021 May 11;22(10). Epub 2021 May 11.

Micalis Institute, AgroParisTech, INRAE, Université Paris-Saclay, 78350 Jouy-en-Josas, France.

Bacterial response to nitric oxide (NO) is of major importance for bacterial survival. NO stress is a main actor of the eukaryotic immune response and several pathogenic bacteria have developed means for detoxification and repair of the damages caused by NO. However, bacterial mechanisms of NO resistance by Gram-positive bacteria are poorly described. Read More

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Heme oxygenase-1 induction by heat shock in rat hepatoma cell line is regulated by the coordinated function of HSF1, NRF2, AND BACH1.

J Biochem 2021 Jun 1. Epub 2021 Jun 1.

Department of Pharmacy, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University 1-1-1 Daigakudohri, Sanyo-onoda-shi 756-0884, Japan.

The mechanism of heme oxygenase-1 (HO-1) induction by heat shock (HS) loading remains unclear. Here, we investigated the contribution of transcription factors to HS-induced HO-1 expression, using a rat hepatoma cell line (H-4-II-E). Our results demonstrated that HS treatment resulted in a marked induction of HO-1. Read More

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Acute Hemolysis and Heme Suppress Anti-CD40 Antibody-Induced Necro-Inflammatory Liver Disease.

Front Immunol 2021 12;12:680855. Epub 2021 May 12.

Division of Internal Medicine, University of Zurich, Zurich, Switzerland.

Clearance of red blood cells and hemoproteins is a key metabolic function of macrophages during hemolytic disorders and following tissue injury. Through this archetypical phagocytic function, heme is detoxified and iron is recycled to support erythropoiesis. Reciprocal interaction of heme metabolism and inflammatory macrophage functions may modify disease outcomes in a broad range of clinical conditions. Read More

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Severe homocysteinemia in two givosiran-treated porphyria patients: is free heme deficiency the culprit?

Ann Hematol 2021 Jul 29;100(7):1685-1693. Epub 2021 May 29.

EPNET Center Munich, Hematology Oncology Center, University of Munich Medical School, Zweibrückenstr.2, 80331, Munich, Germany.

Givosiran is a novel approach to treat patients with acute intermittent porphyrias (AIP) by silencing of ∂-ALA-synthase 1, the first enzyme of heme biosynthesis in the liver. We included two patients in the Envision study who responded clinically well to this treatment. However, in both patients, therapy had to be discontinued because of severe adverse effects: One patient (A) developed local injection reactions which continued to spread all over her body with increasing number of injections and eventually caused a severe systemic allergic reaction. Read More

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Atypical kinetics of cytochrome P450 2J2: Epoxidation of arachidonic acid and reversible inhibition by xenobiotic inhibitors.

Eur J Pharm Sci 2021 May 24;164:105889. Epub 2021 May 24.

Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543. Electronic address:

Extrahepatic CYP2J2 metabolism of arachidonic acid (AA) to bioactive regioisomeric epoxyeicosatrienoic acids (EETs) is implicated in both physiological and pathological conditions. Here, we aimed to characterize atypical substrate inhibition kinetics of this endogenous metabolic pathway and its reversible inhibition by xenobiotic inhibitors when AA is used as the physiologically-relevant substrate vis-à-vis conventional probe substrate astemizole (AST). As compared to typical Michaelis-Menten kinetics observed for AST, complete substrate inhibition was observed for CYP2J2 metabolism of AA to 14,15-EET whereby velocity of the reaction declined significantly at concentrations of AA above 20-30 µM with an estimated substrate inhibition constant (K) of 31 µM. Read More

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Iron supplementation regulates the progression of high fat diet induced obesity and hepatic steatosis via mitochondrial signaling pathways.

Sci Rep 2021 May 24;11(1):10753. Epub 2021 May 24.

Systems Biology Program, Graduate School of Media and Governance, Keio University, 5322, Endo, Fujisawa, Kanagawa, 252-0882, Japan.

Disruption of iron metabolism is closely related to metabolic diseases. Iron deficiency is frequently associated with obesity and hepatic steatosis. However, the effects of iron supplementation on obesity and energy metabolism remain unclear. Read More

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Redox and Inflammatory Signaling, the Unfolded Protein Response, and the Pathogenesis of Pulmonary Hypertension.

Adv Exp Med Biol 2021 ;1304:333-373

Department of Physiology, New York Medical College, Valhalla, NY, USA.

Protein folding overload and oxidative stress disrupt endoplasmic reticulum (ER) homeostasis, generating reactive oxygen species (ROS) and activating the unfolded protein response (UPR). The altered ER redox state induces further ROS production through UPR signaling that balances the cell fates of survival and apoptosis, contributing to pulmonary microvascular inflammation and dysfunction and driving the development of pulmonary hypertension (PH). UPR-induced ROS production through ER calcium release along with NADPH oxidase activity results in endothelial injury and smooth muscle cell (SMC) proliferation. Read More

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Midazolam as a Probe for Drug-Drug Interactions Mediated by CYP3A4: Homotropic Allosteric Mechanism of Site-Specific Hydroxylation.

Biochemistry 2021 Jun 20;60(21):1670-1681. Epub 2021 May 20.

We developed an efficient and sensitive probe for drug-drug interactions mediated by human CYP3A4 by using midazolam (MDZ) as a probe substrate. Using global analysis of four parameters over several experimental data sets, we demonstrate that the first MDZ molecule (MDZ1) binds with high affinity at the productive site near the heme iron and gives only hydroxylation at the 1 position (1OH). The second midazolam molecule (MDZ2) binds at an allosteric site at the membrane surface and perturbs the position and mobility of MDZ1 such that the minor hydroxylation product at the 4 position (4OH) is formed in a 1:2 ratio (35%). Read More

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Protective effects of sodium ferulate on flap transplantation via anti-inflammatory modulation and oxidative stress inhibition.

Braz J Med Biol Res 2021 17;54(7):e10520. Epub 2021 May 17.

Department of Plastic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Ischemia-reperfusion injury (IRI) has brought attention to flap failure in reconstructive surgery. To improve the prognosis of skin transplantation, we performed experimental IRI by surgical obstruction of blood flow and used sodium ferulate (SF) to prevent IRI in rats. After SF treatment, the morphological and histological changes of the skin flaps were observed by H&E and Masson's trichrome staining. Read More

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Strengthened attachment of anammox bacteria on iron-based modified carrier and its effects on anammox performance in integrated floating-film activated sludge (IFFAS) process.

Sci Total Environ 2021 Sep 11;787:147679. Epub 2021 May 11.

Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024, China.

Moving-bed biofilm reactor (MBBR) or integrated floating-film activated sludge (IFFAS) process has been proved to be one of the ideal candidates for anammox application. However, the slow development of anammox bacteria (AnAOB) biofilm and unstable bioactivity always limit their wide application. This study developed a type of novel zero-valent iron (ZVI)-based modified carrier for strengthening AnAOB attachment and enhancing anammox performance. Read More

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September 2021

The Steady March toward Biomimetic Nanoelectronics.

ACS Nano 2021 05 17;15(5):7844-7847. Epub 2021 May 17.

Energy Geosciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California 94720, United States.

Steady progress is being made in unveiling nature's long-range charge transport mechanisms in redox proteins and in the development of versatile self-assembling scaffolds and proteins by design-two separate fields that soon may intersect to yield the first artificial bioelectronic wires. Here, we summarize compelling developments in these areas that put a spotlight on the prospect of their convergence, featuring, in particular, work by Dai in this issue of that illustrates success in intentional design with nuanced control, binding multiple c-type hemes into a specific ordered array bearing the essential hallmarks of heme chains in bacterial multiheme cytochromes. Read More

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Structural modeling of a novel membrane-bound globin-coupled sensor in .

Comput Struct Biotechnol J 2021 26;19:1874-1888. Epub 2021 Mar 26.

Proteinchemistry, Proteomics and Epigenetic Signalling, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Globin-coupled sensors (GCS) usually consist of three domains: a sensor/globin, a linker, and a transmitter domain. The globin domain (GD), activated by ligand binding and/or redox change, induces an intramolecular signal transduction resulting in a response of the transmitter domain. Depending on the nature of the transmitter domain, GCSs can have different activities and functions, including adenylate and di-guanylate cyclase, histidine kinase activity, aerotaxis and/or oxygen sensing function. Read More

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Nitric oxide signaling for actinorhodin production in A3(2) via the DevS/R two-component system.

Appl Environ Microbiol 2021 May 14. Epub 2021 May 14.

From Faculty of Life Sciences, Department of Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka Setagaya-ku, Tokyo 1568502, Japan.

Nitric oxide (NO) is an important signaling molecule in eukaryotic and prokaryotic cells. A previous study revealed an NOS-independent NO production metabolic cycle in which the three nitrogen oxides, nitrate (NO), nitrite (NO) and NO were generated in the actinobacterium A3(2). NO was suggested to act as a signaling molecule, functioning as a hormone that regulates secondary metabolism. Read More

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