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 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.
Zhang
Hai-Gang
HG
Institute of Materia Medica, Faculty of Basic Medicine, Third Military Medical University, Chongqing, China.
Li
Xiao-Hui
XH
Zhou
Jian-Zhi
JZ
Liu
Ya
Y
Jia
Yi
Y
Yuan
Zhi-Bing
ZB
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000494:pharmacology*; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D007930:Leucine / Q000378:metabolism; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D010455:Peptides; D012333:RNA, Messenger; D019204:GTP-Binding Proteins; D007930:Leucine; D002118:Calcium; D009638:Norepinephrine