Protection of cultured human hepatocytes from hydrogen peroxideinduced apoptosis by relaxin3

Abstract

Previous studies have suggested that hepatocyte apoptosis may be a fundamental underlying mechanism of liver injury and diseases, such as liver fibrosis. Relaxin3 has been reported to have antifibrotic actions in the heart and to attenuate isoproterenolinduced myocardial injury; however, the beneficial role of relaxin3 on hepatocyte apoptosis remains to be elucidated. The aim of the present study was to explore the role and possible mechanisms of relaxin3 through hydrogen peroxide (H2O2)induced apoptosis in primary human hepatocytes. Cells were treated with relaxin3 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 caspase3, 8 and 9) and ERS protein markers compared with those of the control group. However, cells treated with relaxin3 (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 H2O2induced apoptosis and relaxin3 treatment. In conclusion, relaxin3 was shown to protect hepatocytes from H2O2induced apoptosis via downregulation of cleaved caspase8 and 9, as well as inhibition of the ERS pathway.