G(alphaq)-protein carboxyl terminus imitation polypeptide GCIP-27 attenuates cardiac hypertrophy in vitro and in vivo.

Abstract

1. Various G(q)-protein-coupled receptors, such as alpha(1)-adrenoceptors, angiotension AT(1) receptors, endothelin ET(A) receptors, neuropeptide Y(1) receptors etc., contribute to cardiac hypertrophy. In G-protein signalling pathways, the carboxyl terminus of the G(alpha) subunit plays a vital role within G-protein-receptor interaction. The present study was designed to explore the effects of the synthetic G(alphaq) carboxyl terminal imitation peptide GCIP-27 on cardiac hypertrophy. 2. Hypertrophy of rat cultured cardiomyocytes was induced by noradrenaline (NA) or angiotensin (Ang) II in vitro. Protein content, [(3)H] incorporation and [Ca(2+)](i) were determined in cardiomyocytes cultured with GCIP-27. Three in vivo animal models of cardiac hypertrophy were prepared using intraperitoneal injections of NA in mice and rats and suprarenal abdominal aortic stenosis in rats. After treatment with GCIP-27 (10-100 microg/L) for 15 or 20 days, indices of cardiac hypertrophy were measured. The effect of GCIP-27 on the mRNA expression of c-fos and c-jun was detected using reverse transcription-polymerase chain reaction. 3. At 10-100 microg/L, GCIP-27 significantly decreased protein content and [(3)H]-leucine incorporation in cultured cardiomyocytes compared with 1 micromol/L NA- and 1 micromol/L AngII-treated groups. After treatment with GCIP-27 (10, 30 or 100 microg/kg) for 15 days, the heart index (HI) and left ventricular index (LVI) in mice decreased significantly compared with the NA control group. In rats, GCIP-27 significantly reduced HI and LVI compared with the NA and aortic stenosis groups. Moreover, [Ca(2+)](i) in cardiomyocytes in the GCIP-27 (3, 10, 30 microg/L)-treated groups was lower than that in the control groups. Expression of c-fos and c-jun mRNA decreased significantly in the myocardium from 5-45 microg/L GCIP-27-treated rats compared with NA controls. 4. The results indicate that GCIP-27 can attenuate cardiac hypertrophy effectively in various models in vitro and in vivo.

• Authors: Hai-Gang Zhang, Xiao-Hui Li, Jian-Zhi Zhou, Ya Liu, Yi Jia, Zhi-Bing Yuan
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 34 Issue 12 Pg. 1276-81 (Dec 2007) ISSN: 0305-1870 [Print] Australia
• PMID: 17973867 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptides
• RNA, Messenger
• GTP-Binding Proteins
• Leucine
• Calcium
• Norepinephrine

Topics

• Animals
• Calcium (metabolism)
• Cardiomegaly (chemically induced, drug therapy, metabolism)
• Cells, Cultured
• GTP-Binding Proteins (pharmacology)
• Genes, fos (genetics)
• Genes, jun (genetics)
• Leucine (metabolism)
• Male
• Mice
• Myocardium (metabolism)
• Myocytes, Cardiac (drug effects, metabolism)
• Norepinephrine
• Peptides (pharmacology)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley