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

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 (HO) elicits ROS that induces skin aging through oxidation of proteins, forming disulfide bridges with cysteine or methionine sulfhydryl groups. Decreased Ca signaling is observed in aged cells, probably secondary to the formation of disulfide bonds among Ca signaling-related proteins. Skin aging processes are modeled by treating keratinocytes with HO. In the present study, HO dose-dependently impaired the adenosine triphosphate (ATP)-induced Ca response, which was partially protected via co-treatment with β-mercaptoethanol, resulting in reduced disulfide bond formation in inositol 1, 4, 5-trisphosphate receptors (IPRs). Molecular hydrogen (H) was found to be more effectively protected HO-induced IPR1 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 can protect oxidation of this process.