Molecular hydrogen protects against oxidative stress-induced SH-SY5Y neuroblastoma cell death through the process of mitohormesis

by Yayoi Murakami, Masafumi Ito, Ikuroh Ohsawa

Inhalation of molecular hydrogen (H₂) gas ameliorates oxidative stress-induced acute injuries in the brain. Consumption of water nearly saturated with H₂ also prevents chronic neurodegenerative diseases including Parkinson’s disease in animal and clinical studies. However, the molecular mechanisms underlying the remarkable effect of a small amount of H₂ remain unclear. Here, we investigated the effect of H₂ on mitochondria in cultured human neuroblastoma SH-SY5Y cells. H₂ increased the mitochondrial membrane potential and the cellular ATP level, which were accompanied by a decrease in the reduced glutathione level and an increase in the superoxide level. Pretreatment with H₂ suppressed H₂O₂-induced cell death, whereas post-treatment did not. Increases in the expression of anti-oxidative enzymes underlying the Nrf2 pathway in H₂-treated cells indicated that mild stress caused by H₂ induced increased resistance to exacerbated oxidative stress. We propose that H₂ functions both as a radical scavenger and a mitohormetic effector against oxidative stress in cells.

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