Growth hormone-releasing hormone promotes survival of cardiac myocytes in vitro and protects against ischaemia-reperfusion injury in rat heart

被引：76

作者：

Granata, Riccarda ^{[1
,2
]}

Trovato, Letizia ^{[1
,2
]}

Gallo, Maria Pia ^{[3
]}

Destefanis, Silvia ^{[1
,2
]}

Settanni, Fabio ^{[1
,2
]}

Scarlatti, Francesca ^{[1
,2
]}

Brero, Alessia ^{[3
]}

Ramella, Roberta ^{[3
]}

Volante, Marco ^{[4
]}

Isgaard, Jorgen ^{[5
]}

Levi, Renzo ^{[3
]}

Papotti, Mauro ^{[4
]}

Alloatti, Giuseppe ^{[3
]}

Ghigo, Ezio ^{[2
]}

机构：

[1] Univ Turin, Lab Mol & Cellular Endocrinol, Dept Internal Med, I-10126 Turin, Italy

[2] Univ Turin, Div Endocrinol & Metab, Dept Internal Med, I-10126 Turin, Italy

[3] Univ Turin, Dept Anim & Human Biol, I-10126 Turin, Italy

[4] Univ Turin, Dept Clin & Biol Sci, San Luigi Hosp, I-10126 Turin, Italy

[5] Univ Gothenburg, Dept Internal Med, Sahlgrenska Acad, Gothenburg, Sweden

来源：

CARDIOVASCULAR RESEARCH | 2009年 / 83卷 / 02期

关键词：

GHRH; Cardioprotection; Cardiac myocyte cell death; Ischaemia; reperfusion injury; MITOGEN-ACTIVATED PROTEIN; PANCREATIC BETA-CELLS; CAMP EARLY REPRESSOR; HUMAN ISLETS; EXPRESSION; APOPTOSIS; RECEPTOR; GHRELIN; CARDIOMYOCYTES; PROLIFERATION;

D O I：

10.1093/cvr/cvp090

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The hypothalamic neuropeptide growth hormone-releasing hormone (GHRH) stimulates GH synthesis and release in the pituitary. GHRH also exerts proliferative effects in extrapituitary cells, whereas GHRH antagonists have been shown to suppress cancer cell proliferation. We investigated GHRH effects on cardiac myocyte cell survival and the underlying signalling mechanisms. Reverse transcriptase-polymerase chain reaction analysis showed GHRH receptor (GHRH-R) mRNA in adult rat ventricular myocytes (ARVMs) and in rat heart H9c2 cells. In ARVMs, GHRH prevented cell death and caspase-3 activation induced by serum starvation and by the beta-adrenergic receptor agonist isoproterenol. The GHRH-R antagonist JV-1-36 abolished GHRH survival action under both experimental conditions. GHRH-induced cardiac cell protection required extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide-3 kinase (PI3K)/Akt activation and adenylyl cyclase/cAMP/protein kinase A signalling. Isoproterenol strongly upregulated the mRNA and protein of the pro-apoptotic inducible cAMP early repressor, whereas GHRH completely blocked this effect. Similar to ARVMs, in H9c2 cardiac cells, GHRH inhibited serum starvation- and isoproterenol-induced cell death and apoptosis through the same signalling pathways. Finally, GHRH improved left ventricular recovery during reperfusion and reduced infarct size in Langendorff-perfused rat hearts, subjected to ischaemia-reperfusion (I/R) injury. These effects involved PI3K/Akt signalling and were inhibited by JV-1-36. Our findings suggest that GHRH promotes cardiac myocyte survival through multiple signalling mechanisms and protects against I/R injury in isolated rat heart, indicating a novel cardioprotective role of this hormone.

引用

页码：303 / 312

页数：10

共 38 条

[31] Cardiotrophin 1 (CT-1) inhibition of cardiac myocyte apoptosis via a mitogen-activated protein kinase-dependent pathway - Divergence from downstream CT-1 signals for myocardial cell hypertrophy [J].