Hydrogen Indirectly Suppresses Increases in Hydrogen Peroxide in Cytoplasmic Hydroxyl Radical-Induced Cells and Suppresses Cellular Senescence
Autor: | Takahiro Sakai, Hirano Shinichi, Ryosuke Kurokawa, Jun Imai |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine Cytoplasm lipid peroxide Eukaryotic Initiation Factor-2 lcsh:Chemistry chemistry.chemical_compound 0302 clinical medicine fluids and secretions cellular senescence Hydrogen peroxide lcsh:QH301-705.5 Spectroscopy Lipid peroxide cytoplasmic hydroxyl radical Chemistry Kinase digestive oral and skin physiology General Medicine Glutathione Computer Science Applications Cell biology Phosphorylation Intracellular Signal Transduction Cyclin-Dependent Kinase Inhibitor p21 hydrogen peroxide digestive system Article Catalysis Inorganic Chemistry 03 medical and health sciences Humans Physical and Theoretical Chemistry Molecular Biology Cyclin-Dependent Kinase Inhibitor p16 Hydroxyl Radical Organic Chemistry Fibroblasts Activating Transcription Factor 4 Oxidative Stress 030104 developmental biology Gene Expression Regulation lcsh:Biology (General) lcsh:QD1-999 Cell culture hydrogen Hydroxyl radical Lipid Peroxidation 030217 neurology & neurosurgery DNA Damage |
Zdroj: | International Journal of Molecular Sciences, Vol 20, Iss 2, p 456 (2019) International Journal of Molecular Sciences Volume 20 Issue 2 |
ISSN: | 1422-0067 |
Popis: | Bacteria inhabiting the human gut metabolize microbiota-accessible carbohydrates (MAC) contained in plant fibers and subsequently release metabolic products. Gut bacteria produce hydrogen (H2), which scavenges the hydroxyl radical (&bull OH). Because H2 diffuses within the cell, it is hypothesized that H2 scavenges cytoplasmic &bull OH (cyto &bull OH) and suppresses cellular senescence. However, the mechanisms of cyto &bull OH-induced cellular senescence and the physiological role of gut bacteria-secreted H2 have not been elucidated. Based on the pyocyanin-stimulated cyto &bull OH-induced cellular senescence model, the mechanism by which cyto &bull OH causes cellular senescence was investigated by adding a supersaturated concentration of H2 into the cell culture medium. Cyto &bull OH-generated lipid peroxide caused glutathione (GSH) and heme shortage, increased hydrogen peroxide (H2O2), and induced cellular senescence via the phosphorylation of ataxia telangiectasia mutated kinase serine 1981 (p-ATMser1981)/p53 serine 15 (p-p53ser15)/p21 and phosphorylation of heme-regulated inhibitor (p-HRI)/phospho-eukaryotic translation initiation factor 2 subunit alpha serine 51 (p-eIF2&alpha )/activating transcription factor 4 (ATF4)/p16 pathways. Further, H2 suppressed increased H2O2 by suppressing cyto &bull OH-mediated lipid peroxide formation and cellular senescence induction via two pathways. H2 produced by gut bacteria diffuses throughout the body to scavenge cyto &bull OH in cells. Therefore, it is highly likely that gut bacteria-produced H2 is involved in intracellular maintenance of the redox state, thereby suppressing cellular senescence and individual aging. Hence, H2 produced by intestinal bacteria may be involved in the suppression of aging. |
Databáze: | OpenAIRE |
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