Hexarelin Protects Rat Cardiomyocytes from Angiotensin II-induced Apoptosis in Vitro

Pang, J., Xu, Rong-Kun, Xu, Xiang-Bin, Cao, Ji-Min, Ni, Chao, Zhu, Wen-Ling, Asotra, Kamlesh, Chen, Meng-Chin, and Chen, C. (2004) Hexarelin Protects Rat Cardiomyocytes from Angiotensin II-induced Apoptosis in Vitro. American Journal of Physiology- Heart And Circulatory Physiology, 286 3: 1063-1069. doi:10.1152/ajpheart.00648.2003

Author Pang, J.
Xu, Rong-Kun
Xu, Xiang-Bin
Cao, Ji-Min
Ni, Chao
Zhu, Wen-Ling
Asotra, Kamlesh
Chen, Meng-Chin,
Chen, C.
Title Hexarelin Protects Rat Cardiomyocytes from Angiotensin II-induced Apoptosis in Vitro
Journal name American Journal of Physiology- Heart And Circulatory Physiology   Check publisher's open access policy
ISSN 0363-6135
Publication date 2004-03
Year available 2003
Sub-type Article (original research)
DOI 10.1152/ajpheart.00648.2003
Volume 286
Issue 3
Start page 1063
End page 1069
Total pages 7
Editor Alberto Nasjletti
Place of publication Washington
Publisher American Physiological Society
Language eng
Subject 110306 Endocrinology
110201 Cardiology (incl. Cardiovascular Diseases)
111201 Cancer Cell Biology
Abstract Loss of cardiomyocytes by apoptosis is proposed to cause heart failure. Angiotensin II (ANG II), an important neurohormonal factor during heart failure, can induce cardiomyocyte apoptosis. Inasmuch as hexarelin has been reported to have protective effects in this process, we examined whether hexarelin can prevent cardiomyocytes from ANG II-induced cell death. Cultured cardiomyocytes from neonatal rats were stimulated with ANG II. Apoptosis was evaluated using fluorescence microscopy, TdT-mediated dUTP nick-end labeling (TUNEL) method, flow cytometry, DNA laddering, and analysis of cell viability by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). It was found that incubation with 0.1 µmol/l ANG II for 48 h increased cardiomyocyte apoptosis. Administration of 0.1 µmol/l hexarelin significantly decreased this ANG II-induced apoptosis and DNA fragmentation and increased myocyte viability. To further investigate the underlying mechanisms, caspase-3 activity assay and mRNA expression of Bax, Bcl-2, and growth hormone secretagogue receptor (GHS-R; the supposed hexarelin binding site) were examined. GHS-R mRNA was abundantly expressed in cardiomyocytes and was upregulated after administration of hexarelin. These results suggest that hexarelin abates cardiomyocytes from ANG II-induced apoptosis possibly via inhibiting the increased caspase-3 activity and Bax expression induced by ANG II and by increasing the expression of Bcl-2, which is depressed by ANG II. Whether the upregulated expression of GHS-R induced by hexarelin is associated with this antiapoptotic effect deserves further investigation.
Keyword Growth-hormone Secretagogues
cell death
heart failure
Q-Index Code C1
Additional Notes First published December 11, 2003

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
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