ZAK induces cardiomyocyte hypertrophy and brain natriuretic peptide expression via p38/JNK signaling and GATA4/c-Jun transcriptional factor activation

doi:10.1007/s11010-015-2389-z

CNU IR > College of Smart Living > Dept. of Hospital and Health (including master's program) > Periodical Articles > Item 310902800/29647

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Title:	ZAK induces cardiomyocyte hypertrophy and brain natriuretic peptide expression via p38/JNK signaling and GATA4/c-Jun transcriptional factor activation
Authors:	Hsieh, You-Liang Tsai, Ying-Lan Shibu, Marthandam Asokan Su, Chia-chi Chung, Li-Chin Pai, Peiying Kuo, Chia-Hua Yeh, Yu-Lan Viswanadha, Vijaya Padma Huang, Chih-Yang
Contributors:	醫務管理系
Keywords:	Cardiac hypertrophy Sterile alpha motif and leucine zipper containing kinase Mixed lineage kinase
Date:	2015-07
Issue Date:	2016-04-19 19:03:13 (UTC+8)
Publisher:	Springer
Abstract:	Cardiomyocyte hypertrophy is an adaptive response of heart to various stress conditions. During the period of stress accumulation, transition from physiological hypertrophy to pathological hypertrophy results in the promotion of heart failure. Our previous studies found that ZAK, a sterile alpha motif and leucine zipper containing kinase, was highly expressed in infarcted human hearts and demonstrated that overexpression of ZAK induced cardiac hypertrophy. This study evaluates, cellular events associated with the expression of two doxycycline (Dox) inducible Tet-on ZAK expression systems, a Tet-on ZAK WT (wild-type), and a Tet-on ZAK DN (mutant, Dominant-negative form) in H9c2 myoblast cells; Tet-on ZAK WT was found to increase cell size and hypertrophic marker BNP in a dose-dependent manner. To ascertain the mechanism of ZAK-mediated hypertrophy, expression analysis with various inhibitors of the related upstream and downstream proteins was performed. Tet-on ZAK WT expression triggered the p38 and JNK pathway and also activated the expression and nuclear translocation of p-GATA4 and p-c-Jun transcription factors, without the involvement of p-ERK or NFATc3. However, Tet-on ZAK DN showed no effect on the p38 and JNK signaling cascade. The results showed that the inhibitors of JNK1/2 and p38 significantly suppressed ZAK-induced BNP expression. The results show the role of ZAK and/or the ZAK downstream events such as JNK and p38 phosphorylation, c-Jun, and GATA-4 nuclear translocation in cardiac hypertrophy. ZAK and/or the ZAK downstream p38, and JNK pathway could therefore be potential targets to ameliorate cardiac hypertrophy symptoms in ZAK-overexpressed patients.
Relation:	Molecular And Cellular Biochemistry, v.405 n.1-2, pp.1-9
Appears in Collections:	[Dept. of Hospital and Health (including master's program)] Periodical Articles

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