Hydrogen gas protects IP3Rs by reducing disulfide bridges in human keratinocytes under oxidative stress

<jats:title>Abstract</jats:title><jats:p>Based on the oxidative stress theory, aging derives from the accumulation of oxidized proteins induced by reactive oxygen species (ROS) in the cytoplasm. Hydrogen peroxide (H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>) elicits ROS that induces skin aging through oxidation of proteins, forming disulfide bridges with cysteine or methionine sulfhydryl groups. Decreased Ca<jats:sup>2+</jats:sup> signaling is observed in aged cells, probably secondary to the formation of disulfide bonds among Ca<jats:sup>2+</jats:sup> signaling-related proteins. Skin aging processes are modeled by treating keratinocytes with H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>. In the present study, H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> dose-dependently impaired the adenosine triphosphate (ATP)-induced Ca<jats:sup>2+</jats:sup> response, which was partially protected via co-treatment with β-mercaptoethanol, resulting in reduced disulfide bond formation in inositol 1, 4, 5-trisphosphate receptors (IP<jats:sub>3</jats:sub>Rs). Molecular hydrogen (H<jats:sub>2</jats:sub>) was found to be more effectively protected H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>-induced IP<jats:sub>3</jats:sub>R1 dysfunction by reducing disulfide bonds, rather than quenching ROS. In conclusion, skin aging processes may involve ROS-induced protein dysfunction due to disulfide bond formation, and H<jats:sub>2</jats:sub> can protect oxidation of this process.</jats:p>