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

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...

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Published in:Clinical and experimental pharmacology & physiology 2007-12, Vol.34 (12), p.1276
Main Authors: Zhang, Hai-Gang, Li, Xiao-Hui, Zhou, Jian-Zhi, Liu, Ya, Jia, Yi, Yuan, Zhi-Bing
Format: Article
Language:English
Subjects:
Animals
Calcium - metabolism
Cardiomegaly - chemically induced
Cardiomegaly - drug therapy
Cardiomegaly - metabolism
Cells, Cultured
Genes, fos - genetics
Genes, jun - genetics
GTP-Binding Proteins - pharmacology
Leucine - metabolism
Male
Mice
Myocardium - metabolism
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Norepinephrine
Peptides - pharmacology
Rats
Rats, Sprague-Dawley
RNA, Messenger - metabolism
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Summary: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.
ISSN:0305-1870
1440-1681
DOI:10.1111/j.1440-1681.2007.04716.x