tailieunhanh - Báo cáo khoa học: The gp130⁄STAT3 signaling pathway mediates b-adrenergic receptor-induced atrial natriuretic factor expression in cardiomyocytes

b-Adrenergic receptor (b-AR)-induced cardiac remodeling is closely linked with the re-expression of the atrial natriuretic factor (ANF) gene. How-ever, the exact molecular mechanism of this response remains elusive. Here, we demonstrate that theb-AR agonist isoproterenol potently evokes the tyrosine phosphorylation of STAT3 and increases its transcriptional. | ễFEBS Journal The gp130 STAT3 signaling pathway mediates b-adrenergic receptor-induced atrial natriuretic factor expression in cardiomyocytes Hui Zhang Wei Feng Wenqiang Liao Xiaowei Ma Qide Han and Youyi Zhang Institute of Vascular Medicine Peking University Third Hospitaland Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Beijing China Keywords ANF b-adrenergic receptor cardiomyocytes gp130 STAT3 Correspondence Y. Zhang Institute of Vascular Medicine Peking University Third Hospital Beijing 100083 China Fax 86 10 62361450 Tel 86 10 82802306 E-mail zhangyy@ Received 31 March 2008 revised 8 May 2008 accepted 13 May 2008 b-Adrenergic receptor b-AR -induced cardiac remodeling is closely linked with the re-expression of the atrial natriuretic factor ANF gene. However the exact molecular mechanism of this response remains elusive. Here we demonstrate that the b-AR agonist isoproterenol potently evokes the tyrosine phosphorylation of STAT3 and increases its transcriptional activity in an extracellularly regulated kinase 1 2 and glycoprotein gp 130 signaling-dependent manner in rat cardiomyocytes. Interestingly both specific silencing of signal transducers and activators of transcription 3 STAT3 expression by lentivirus-mediated RNA interference and antagonism of gp130 signaling lead to significant inhibition of isoproterenol-stimulated ANF expression. Together these results indicate that gp130 STAT3 signaling has an essential role in ANF expression by b-AR stimulation. doi b-Adrenergic receptor b-AR an archetypal member of the G-protein-coupled receptor GPCR superfamily has roles in a variety of cardiovascular pathological and physiological processes. There are three known subtypes in the heart - b -AR. b2-AR and b3-AR. Of these the b1-AR subtype stimulates the classic Gs-adenylyl cyclase-cAMP-protein kinase A signaling pathway whereas b2-AR activates bifurcated signaling pathways through both Gs and