title: 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.affiliation: The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No.23, YouZheng Road, NanGang District, Harbin 150001, Heilongjiang Province, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Department of Gastroenterology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.affiliation: The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No.23, YouZheng Road, NanGang District, Harbin 150001, Heilongjiang Province, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhao
authors.affiliation: The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No.23, YouZheng Road, NanGang District, Harbin 150001, Heilongjiang Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No.23, YouZheng Road, NanGang District, Harbin 150001, Heilongjiang Province, China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Chi
authors.affiliation: The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No.23, YouZheng Road, NanGang District, Harbin 150001, Heilongjiang Province, China.
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Liu
authors.affiliation: The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No.23, YouZheng Road, NanGang District, Harbin 150001, Heilongjiang Province, China.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Chen
authors.affiliation: The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No.23, YouZheng Road, NanGang District, Harbin 150001, Heilongjiang Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.affiliation: The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No.23, YouZheng Road, NanGang District, Harbin 150001, Heilongjiang Province, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No.23, YouZheng Road, NanGang District, Harbin 150001, Heilongjiang Province, China. Electronic address: xinhua_yin@163.com.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Yin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology*; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012065:Relaxin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D012065:Relaxin; D005947:Glucose
keywords: Apoptosis; Endoplasmic reticulum stress; H2 relaxin; H3 relaxin; High glucose