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Open AccessArticle

Hydrogen Indirectly Suppresses Increases in Hydrogen Peroxide in Cytoplasmic Hydroxyl Radical-Induced Cells and Suppresses Cellular Senescence

1
Laboratory of Physiological Chemistry, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki, Gunma 370-0033, Japan
2
MiZ Co., Ltd., 2-19-15 Ofuna, Kamakura, Kanagawa 247-0056, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(2), 456; https://doi.org/10.3390/ijms20020456
Received: 15 December 2018 / Revised: 16 January 2019 / Accepted: 18 January 2019 / Published: 21 January 2019
(This article belongs to the Special Issue Nutrition and Aging)
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 (•OH). Because H2 diffuses within the cell, it is hypothesized that H2 scavenges cytoplasmic •OH (cyto •OH) and suppresses cellular senescence. However, the mechanisms of cyto •OH-induced cellular senescence and the physiological role of gut bacteria-secreted H2 have not been elucidated. Based on the pyocyanin-stimulated cyto •OH-induced cellular senescence model, the mechanism by which cyto •OH causes cellular senescence was investigated by adding a supersaturated concentration of H2 into the cell culture medium. Cyto •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-eIF2α)/activating transcription factor 4 (ATF4)/p16 pathways. Further, H2 suppressed increased H2O2 by suppressing cyto •OH-mediated lipid peroxide formation and cellular senescence induction via two pathways. H2 produced by gut bacteria diffuses throughout the body to scavenge cyto •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. View Full-Text
Keywords: cytoplasmic hydroxyl radical; hydrogen; hydrogen peroxide; lipid peroxide; cellular senescence cytoplasmic hydroxyl radical; hydrogen; hydrogen peroxide; lipid peroxide; cellular senescence
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Sakai, T.; Kurokawa, R.; Hirano, S.-I.; Imai, J. Hydrogen Indirectly Suppresses Increases in Hydrogen Peroxide in Cytoplasmic Hydroxyl Radical-Induced Cells and Suppresses Cellular Senescence. Int. J. Mol. Sci. 2019, 20, 456.

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