PKCζ interacts with STAT3 and promotes its activation in cardiomyocyte hypertrophy

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• 作者：Jingyan Li^a ; ¹ ; Hui Gao^a ; ^b ; ¹ ; Junying Huang^a ; Panxia Wang^a ; Yi Huang^a ; Wenwei Luo^a ; Xiaoying Zhang^a ; Peiye Shen^a ; Jia You^a ; Sidong Cai^a ; Zhuoming Li^a ; ^{lizhm5@mail.sysu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Peiqing Liu^a ; ^{liupq@mail.sysu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Cardiac hypertrophy ; Phenylephrine ; PKCζ ; STAT3 ; Phosphorylation
• 刊名：Journal of Pharmacological Sciences
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：132
• 期：1
• 页码：15-23
• 全文大小：2005 K

文摘

This study was aimed to investigate the crosstalk between protein kinase C ζ (PKCζ) and signal transducer and activator of transcription 3 (STAT3) in cardiomyocyte hypertrophy. In neonatal rat cardiomyocyte hypertrophic model induced by phenylephrine (PE), the levels of phosphorylated PKCζ and phosphorylated STAT3 were significantly increased, suggesting the activation of both PKCζ and STAT3 in cardiomyocyte hypertrophy. Overexpression of PKCζ by adenovirus infection elevated the expressions of hypertrophic markers atrial natriuretic factor (ANF) and brains natriuretic polypeptide (BNP), as well as the cell surface area; while genetic silencing of PKCζ inhibited PE-induced cardiomyocyte hypertrophy. An interaction between PKCζ and STAT3 in cardiomyocytes was shown by co-immunoprecipitation experiments. Overexpression of PKCζ increased the phosphorylated level of STAT3 at both Ser727 and Tyr705, promoted the nuclear translocation of STAT3, and enhanced the expression of STAT3 downstream target genes c-fos and angiotensinogen (aGT); whereas PKCζ knockdown prevented PE-induced STAT3 activation, nuclear shuttling and transcriptional activation. In conclusion, PKCζ interacts with STAT3 and promotes its activation in cardiomyocyte hypertrophy. Strategies targeting inhibition of PKCζ-STAT3 signaling pathway suggest a therapeutic potential for cardiac hypertrophy.