H2 and H3 relaxin inhibit high glucose-induced apoptosis in neonatal rat ventricular myocytes.

Abstract

High concentrations of glucose induce cardiomyocyte apoptosis, and contribute to diabetic cardiomyopathy. Relaxin-2 and relaxin-3 are two members of the relaxin peptide family that are cardioprotective. However, it remains unknown whether relaxin-2 or relaxin-3 can regulate apoptosis in high glucose treated-neonatal rat ventricular myocytes (NRVMs). In cultured NRVMs, 33 mmol/l high glucose (HG) increased apoptosis in a time-dependent manner. HG-increased the protein expression of cleaved caspase-8 and -9, two initiators of the extrinsic and intrinsic pathways of apoptosis, Caspase-3 was attenuated by human recombinant relaxin-2 (H2 relaxin) or relaxin-3 (H3 relaxin), indicating that H2 and H3 relaxin inhibited HG-induced apoptosis. Furthermore, endoplasmic reticulum stress (ERS) markers CHOP and caspase-12 were markedly increased in HG-treated NRVMs, leading to apoptosis; this effect was also effectively attenuated by H2 relaxin or H3 relaxin. Treatment of NRVMs with HG reduced autophagy which cannot be adjusted by H2 relaxin or H3 relaxin. In conclusion, HG-induced apoptosis in NRVMs was mediated, in part, by the activation of the extrinsic and intrinsic pathways of apoptosis and ERS, all inhibited by H2 relaxin or H3 relaxin.

• Authors: Xiaohui Zhang, Xiao Ma, Meng Zhao, Bo Zhang, Jinyu Chi, Wenxiu Liu, Wenjia Chen, Yu Fu, Yue Liu, Xinhua Yin
• Journal: Biochimie (Biochimie) Vol. 108 Pg. 59-67 (Jan 2015) ISSN: 1638-6183 [Electronic] France
• PMID: 25446652 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

Chemical References

• Relaxin
• Glucose

Topics

• Animals
• Animals, Newborn
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Dose-Response Relationship, Drug
• Endoplasmic Reticulum Stress (drug effects)
• Female
• Glucose (pharmacology)
• Heart Ventricles (cytology)
• Male
• Myocytes, Cardiac (cytology, drug effects)
• Rats
• Rats, Wistar
• Relaxin (pharmacology)
• Signal Transduction (drug effects)