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

PLoS One. 2017 May 3;12(5):e0176992. doi: 10.1371/journal.pone.0176992. eCollection 2017.


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.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Blotting, Western
  • Cell Death / drug effects*
  • Cell Death / physiology
  • Cell Line, Tumor
  • DNA, Mitochondrial / metabolism
  • Dose-Response Relationship, Drug
  • Humans
  • Hydrogen / pharmacology*
  • Membrane Potential, Mitochondrial / drug effects
  • Neuroblastoma / metabolism*
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Oxygen Consumption / drug effects


  • DNA, Mitochondrial
  • Hydrogen
  • Adenosine Triphosphate

Grant support

This work was supported in part by Japan Society for the Promotion of Science (JSPS) KAKENHI ( Grant Number 24500882 and 16H03267 for IO. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.