| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Department of Physiology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005; 2Division of Cardiology, Department of Medicine, Peking Union Hospital, Beijing 100005, China; 3Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048-1865; 4Endocrine Cell Biology, Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia
Submitted 10 July 2003 ; accepted in final form 4 November 2003
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.
growth hormone secretagogues; cell death; heart failure
This article has been cited by other articles:
|
|
 |
|
  E. Q. Haxhija, H. Yang, A. U. Spencer, H. Koga, X. Sun, and D. H. Teitelbaum Modulation of mouse intestinal epithelial cell turnover in the absence of angiotensin converting enzyme Am J Physiol Gastrointest Liver Physiol, July 1, 2008; 295(1): G88 - G98. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Xu, J. Pang, H. Yin, M. Li, W. Hao, C. Chen, and J.-M. Cao Hexarelin suppresses cardiac fibroblast proliferation and collagen synthesis in rat Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2952 - H2958. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Shimojo, S. Jesmin, S. Zaedi, M. Soma, S. Maeda, I. Yamaguchi, K. Goto, and T. Miyauchi Changes in important apoptosis-related molecules in the endothelin-1-induced hypertrophied cardiomyocytes: effect of the pretreatment with eicosapentaenoic Acid. Experimental Biology and Medicine, June 1, 2006; 231(6): 932 - 936. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-B. Xu, J.-J. Pang, J.-M. Cao, C. Ni, R.-K. Xu, X.-Z. Peng, X.-X. Yu, S. Guo, M.-C. Chen, and C. Chen GH-releasing peptides improve cardiac dysfunction and cachexia and suppress stress-related hormones and cardiomyocyte apoptosis in rats with heart failure Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1643 - H1651. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
