title: Protection of cultured human hepatocytes from hydrogen peroxide‑induced apoptosis by relaxin‑3.
abstract: Previous studies have suggested that hepatocyte apoptosis may be a fundamental underlying mechanism of liver injury and diseases, such as liver fibrosis. Relaxin‑3 has been reported to have anti‑fibrotic actions in the heart and to attenuate isoproterenol‑induced myocardial injury; however, the beneficial role of relaxin‑3 on hepatocyte apoptosis remains to be elucidated. The aim of the present study was to explore the role and possible mechanisms of relaxin‑3 through hydrogen peroxide (H2O2)‑induced apoptosis in primary human hepatocytes. Cells were treated with relaxin‑3 and then cell viability, morphological features, the presence of cleaved caspases as well as the levels of endoplasmic reticulum stress (ERS) protein markers and autophagy markers were evaluated. The H2O2 group showed significantly decreased cell viability, increased apoptosis as well as upregulation of caspases (cleaved caspase‑3, ‑8 and ‑9) and ERS protein markers compared with those of the control group. However, cells treated with relaxin‑3 (10 ng/ml) demonstrated improved cell viability, reduced apoptosis and decreased expression of cleaved caspases and ERS markers. However, the expression of autophagy markers remained unchanged following H2O2‑induced apoptosis and relaxin‑3 treatment. In conclusion, relaxin‑3 was shown to protect hepatocytes from H2O2‑induced apoptosis via downregulation of cleaved caspase‑8 and ‑9, as well as inhibition of the ERS pathway.
authors.affiliation: Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Microbiology and Parasitology, The Heilongjiang Key Laboratory of Immunity and Infection, Pathogenic Biology, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Su
authors.initials: S
authors.lastname: Han
authors.affiliation: Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Fan
authors.affiliation: Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Ming-Na
authors.initials: MN
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Ai-Yun
authors.initials: AY
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Bing-Rong
authors.initials: BR
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D020011:Protective Agents / Q000494:pharmacology*; D012065:Relaxin / Q000494:pharmacology*
chemical_list: D020011:Protective Agents; D012065:Relaxin; D006861:Hydrogen Peroxide; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9