How Hydrogen Helps Cells Fight Stress and Stay Healthy
- Authors
- Tomoya Hasegawa, Mikako Ito, Satoru Hasegawa, Kouki Takeda, Hiroshi Nishiwaki, Shuto Negishi, Kinji Ohno
- Journal
- The FASEB Journal
- Year
- 2020
- DOI
- 10.1096/fasebj.2020.34.s1.09226
- Study Type
- Cell Culture
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- Japan
- Health Condition
- Parkinson's Disease
- Body System
- Cellular
TL;DR
Molecular hydrogen helps protect cells by boosting their stress response system, particularly in cells with active energy-producing structures, and may aid in treating diseases linked to oxidative damage.
Key Finding
Molecular hydrogen activates a cellular stress-response system (mtUPR) that helps protect mitochondria, but only in cells with high energy-production activity.
Summary
Researchers studied how molecular hydrogen (H2) affects mitochondria, which are the energy-producing structures inside cells. They found that hydrogen water and hydrogen gas activated a cellular stress-response system called the mitochondrial unfolded protein response (mtUPR), which helps cells cope with damage. However, this effect only occurred in certain types of cells—specifically those with more active energy-production machinery. The study was conducted in mice and laboratory cell cultures, not in humans.
Practical Takeaway
This laboratory study suggests a potential mechanism for how hydrogen might help with oxidative stress-related conditions, but it is limited to cell cultures and animal models. Much more research, including human studies, would be needed before drawing conclusions about hydrogen water's effects on human health or disease.
Abstract
Molecular hydrogen (H 2 ) has an anti‐oxidant effect on hundreds of animal models. However, the exact molecular mechanisms of molecular hydrogen still remains elusive. Mitochondrial unfolded protein response (mtUPR) is a known stress response to perturbed mitochondrial proteostasis caused by oxidative stress or mitochondrial dysfunction. We examined the effects of molecular hydrogen on mtUPR by examining mtUPR‐related protein expression in vivo and in vitro. Mice drinking hydrogen water showed higher expression of the HSP60 chaperone protein, which is an mtUPR marker, as well as other mtUPR‐related proteins including protein kinase R (PKR), phosphorylated eukaryotic translation initiation factor 2a (eIf2a), and activating transcription factor 5 (ATF5). Incubation of cultured cells in 10% hydrogen gas increased expression of HSP60 and some mtUPR‐related proteins in four human cell lines (A549, HeLa, HT1080, and PC3 cells, which are called “responders” hereafter), but not in three other human cell lines (HCT116, HepG2, and SH‐SY5Y cells, which are called “non‐responders”). Flowcytometric analysis disclosed that higher mitochondrial mass, higher superoxide production, higher mitochondrial membrane potential in “responders” compared to “non‐responders’. Similarly, measurement of the oxygen consumption rate revealed high spare capacity of the electron transport complex (ETC) activity in “responders”. Indeed, the gene set enrichment analysis (GSEA) of gene expression profiles in gene expression omnibus (GEO) of two groups of cell lines demonstrated that ETC‐related pathways were upregulated in “responders”. In addition, quantification of DNA synthesis by BrdU assay revealed that incubation of cultured cells in 10% hydrogen gas for 48 h induced cell proliferation, and rescued proliferation blockage by rotenone in “responders”. We report that hydrogen induces mtUPR and cellular proliferation in cell lines with higher mitochondrial ETC activity. Molecular hydrogen ameliorates a variety of diseases including Parkinson’s disease, myocardiac or cerebral infarction, and inflammatory diseases. Molecular hydrogen is thus likely to manage mitochondrial stress through activation of mtUPR, and exerts its effects on these oxidative stress‐related diseases. Support or Funding Information This research was supported by grants‐in‐aids from MEXT, MHLW, and AMED of Japan.