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Published on: September 18, 2017
H2 and H3 relaxin inhibit high glucose-induced apoptosis in neonatal rat ventricular myocytes
Xiaohui Zhang1, Xiao Ma2, Meng Zhao1
1The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No.23, YouZheng Road, NanGang District, Harbin 150001, Heilongjiang Province, China.
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.
Insights
High glucose induces heart cell death via apoptosis and endoplasmic reticulum stress. Both relaxin-2 and relaxin-3 protect against this damage by inhibiting key apoptotic pathways.
Area of Science:
- Cardiology
- Molecular Biology
- Endocrinology
Background:
- High glucose concentrations induce cardiomyocyte apoptosis, contributing to diabetic cardiomyopathy.
- Relaxin-2 and relaxin-3 are cardioprotective peptides, but their role in high glucose-induced apoptosis is unknown.
Purpose of the Study:
- To investigate the effects of relaxin-2 and relaxin-3 on high glucose-induced apoptosis in neonatal rat ventricular myocytes (NRVMs).
Main Methods:
- NRVMs were treated with high glucose (33 mmol/l) for varying times.
- Apoptosis was assessed by measuring cleaved caspase-8, -9, and -3 expression.
- Endoplasmic reticulum stress markers (CHOP, caspase-12) and autophagy were also evaluated.
- Effects of human recombinant relaxin-2 (H2 relaxin) and relaxin-3 (H3 relaxin) were examined.
Main Results:
- High glucose increased apoptosis in NRVMs in a time-dependent manner.
- H2 relaxin and H3 relaxin attenuated high glucose-induced apoptosis.
- High glucose elevated endoplasmic reticulum stress markers, which were reduced by H2 and H3 relaxin.
- High glucose reduced autophagy, an effect not modulated by H2 or H3 relaxin.
Conclusions:
- High glucose-induced apoptosis in NRVMs involves activation of extrinsic and intrinsic apoptotic pathways and endoplasmic reticulum stress.
- Relaxin-2 and relaxin-3 effectively inhibit these pathways, offering cardioprotection in a high glucose environment.
