PKCζ interacts with STAT3 and promotes its activation in cardiomyocyte hypertrophy
PKCζ interacts with STAT3 and promotes its activation in cardiomyocyte hypertrophy
复制标题
PKCzeta 与 STAT3 相互作用并促进其在心肌细胞肥大中的激活。
DOI：
10.1016/j.jphs.2016.03.010
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发表时间：
2016-09-01
影响因子：
3.5
通讯作者：
Liu, Peiqing
中科院分区：
文献类型：
--
作者：
Li, Jingyan;Gao, Hui;Liu, Peiqing
This study was aimed to investigate the crosstalk between protein kinase C zeta (PKC zeta) 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 PKC zeta and phosphorylated STAT3 were significantly increased, suggesting the activation of both PKC zeta and STAT3 in cardiomyocyte hypertrophy. Overexpression of PKC zeta 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 PKC zeta inhibited PE-induced cardiomyocyte hypertrophy. An interaction between PKC zeta and STAT3 in cardiomyocytes was shown by co-immunoprecipitation experiments. Overexpression of PKC zeta 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 PKC zeta knockdown prevented PE-induced STAT3 activation, nuclear shuttling and transcriptional activation. In conclusion, PKC zeta interacts with STAT3 and promotes its activation in cardiomyocyte hypertrophy. Strategies targeting inhibition of PKC zeta-STAT3 signaling pathway suggest a therapeutic potential for cardiac hypertrophy. (C) 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license
