Salusins protect neonatal rat cardiomyocytes from serum deprivation-induced cell death through upregulation of GRP78.

Abstract

Salusin-alpha and salusin-beta are newly identified bioactive peptides with hemodynamic and mitogenic activities. Recent studies have shown that salusins improve calcium uptake and protein synthesis in neonatal rat cardiomyocytes, suggesting that salusins may be regulatory factors for myocardial growth and hypertrophy. In this study, we investigated whether salusins improve the survival of cardiomyocytes after serum deprivation. Cultured neonatal cardiomyocytes were treated with or without salusins (salusin-alpha or salusin-beta) at a concentration range of 10 to 10 mol/L for 24 h under serum deprivation conditions. Cardiomyocytes viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazonium bromide assay. Cell death or apoptosis rate was identified by flow cytometry analysis. Compared to serum deprivation-only groups, cardiomyocyte viability was significantly increased in salusin-alpha or salusin-beta groups. Cell death rate was decreased after administration of 10 mol/L salusin-alpha or salusin-beta. Salusin-beta was able to decrease the apoptotic rate. Salusins also increased the expression of cardiomyocyte glucose-regulated protein 78 (GRP78) as estimated by Western blot. Furthermore, antisense oligodeoxynucleotide specifically against GRP78 attenuated or abrogated antiapoptosis or survival effects of salusin-beta. These findings suggest that salusin-alpha and salusin-beta may be a potential survival factor against serum deprivation-induced myocardial cell death and that this cardioprotective effect may involve an upregulation of GRP78 expression in cardiomyocytes.

• Authors: Yan Xiao-Hong, Lin Li, Pan Yan-Xia, Lu Hong, Rong Wei-Fang, Lu Yan, Ren An-Jing, Tang Chao-Shu, Yuan Wen-Jun
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 48 Issue 2 Pg. 41-6 (Aug 2006) ISSN: 0160-2446 [Print] United States
• PMID: 16954820 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media, Serum-Free
• Endoplasmic Reticulum Chaperone BiP
• GRP78 protein, rat
• HSPA5 protein, human
• Heat-Shock Proteins
• Intercellular Signaling Peptides and Proteins
• Molecular Chaperones
• Oligonucleotides, Antisense
• TOR2A protein, human
• Adenosine Triphosphatases

Topics

• Adenosine Triphosphatases (pharmacology)
• Animals
• Animals, Newborn
• Apoptosis
• Cells, Cultured
• Culture Media, Serum-Free
• Cytoprotection
• Endoplasmic Reticulum Chaperone BiP
• Heat-Shock Proteins (analysis, physiology)
• Intercellular Signaling Peptides and Proteins
• Molecular Chaperones (analysis, physiology)
• Myocytes, Cardiac (cytology, drug effects)
• Oligonucleotides, Antisense (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Up-Regulation