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G αq ‐PROTEIN CARBOXYL TERMINUS IMITATION POLYPEPTIDE GCIP‐27 ATTENUATES CARDIAC HYPERTROPHY IN VITRO AND IN VIVO
Author(s) -
Zhang HaiGang,
Li XiaoHui,
Zhou JianZhi,
Liu Ya,
Jia Yi,
Yuan ZhiBing
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04716.x
Subject(s) - in vivo , in vitro , cardiac hypertrophy , n terminus , imitation , muscle hypertrophy , chemistry , medicine , protein biosynthesis , microbiology and biotechnology , endocrinology , biochemistry , biology , peptide sequence , neuroscience , gene , genetics
SUMMARY1 Various G q ‐protein‐coupled receptors, such as α 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 α subunit plays a vital role within G‐protein–receptor interaction. The present study was designed to explore the effects of the synthetic G αq 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 µg/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 µg/L, GCIP‐27 significantly decreased protein content and [ 3 H]‐leucine incorporation in cultured cardiomyocytes compared with 1 µmol/L NA‐ and 1 µmol/L AngII‐treated groups. After treatment with GCIP‐27 (10, 30 or 100 µg/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 µg/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 µg/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 .