Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators

Abstract

We previously showed that H2 acts as a novel antioxidant to protect cells against oxidative stress. Subsequently, numerous studies have indicated the potential applications of H2 in therapeutic and preventive medicine. Moreover, H2 regulates various signal transduction pathways and the expression of many genes. However, the primary targets of H2 in the signal transduction pathways are unknown. Here, we attempted to determine how H2 regulates gene expression. In a pure chemical system, H2 gas (approximately 1%, v/v) suppressed the autoxidation of linoleic acid that proceeds by a free radical chain reaction, and pure 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine (PAPC), one of the major phospholipids, was autoxidized in the presence or absence of H2. H2 modified the chemical production of the autoxidized phospholipid species in the cell-free system. Exposure of cultured cells to the H2-dependently autoxidized phospholipid species reduced Ca2+ signal transduction and mediated the expression of various genes as revealed by comprehensive microarray analysis. In the cultured cells, H2 suppressed free radical chain reaction-dependent peroxidation and recovered the increased cellular Ca2+, resulting in the regulation of Ca2+-dependent gene expression. Thus, H2 might regulate gene expression via the Ca2+ signal transduction pathway by modifying the free radical-dependent generation of oxidized phospholipid mediators.

Linking hydrogen-mediated boron toxicity tolerance with improvement of root elongation, water status and reactive oxygen species balance: a case study for rice

“…Ohsawa et al, 2007;Buchholz et al, 2008;Huang et al, 2010;Taura et al, 2010;Kawaguchi et al, 2014;Iuchi et al, 2016), and proved that H 2 could react directly with cytotoxic ROS due to its ability to rapidly diffuse across membranes (Ohsawa et al, 2007;Taura et al, 2010;Iuchi et al, 2016). Consistently, in our experiments, H 2 alleviated B-induced lipid peroxidation and H 2 O 2 overproduction (Fig.…”

“…Ample evidence further confirmed that H 2 exhibits potential as a new antioxidant and signalling molecule in preventive and therapeutic applications (e.g. Huang et al, 2010;Kawaguchi et al, 2014;Iuchi et al, 2016). Similar to the approach used in animals, hydrogen-rich water was regarded as a safe and easily available means of investigating the physiological function of endogenous H 2 in plants.…”

Hydrogen Flush After Cold Storage as a New End‐Ischemic Ex Vivo Treatment for Liver Grafts Against Ischemia/Reperfusion Injury

“…Since the first report in 2007, (5) accumulating evidence has demonstrated its therapeutic potential against IRI and the underlying mechanisms therein. Currently, H 2 i s known to have 3 definitive effects: antioxidant, (5)(6)(7)(8)(9)(10)(11)(12)(13) anti-inflammatory, (10,(14)(15)(16) and antiapoptosis. (8,17) Though some experimental animal studies have shown its therapeutic potential in organ preservation, eg, lung, (11) heart, (18) kidney, (6) intestine, (7) and liver, (19,20) its clinical use is yet to be applied because of its unfavorable features.…”

Molecular Hydrogen as a Neuroprotective Agent

“…Recently, Iuchi et al demonstrated that low concentrations (approximately 1%, v/v) of H 2 modulate Ca 2+ signal transduction and regulate gene expression by modifying the production of oxidized phospholipid species [105]. Because H 2 is the smallest as well as a nonpolar molecule, it is unlikely that H 2 could bind to some protein mediators.…”