caa a22 4500 606234446 CHVBK 20210128101237.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s11010-015-2389-z doi (NATIONALLICENCE)springer-10.1007/s11010-015-2389-z ZAK induces cardiomyocyte hypertrophy and brain natriuretic peptide expression via p38/JNK signaling and GATA4/c-Jun transcriptional factor activation [Elektronische Daten] [You-Liang Hsieh, Ying-Lan Tsai, Marthandam Shibu, Chia-chi Su, Li-Chin Chung, Peiying Pai, Chia-Hua Kuo, Yu-Lan Yeh, Vijaya Viswanadha, Chih-Yang Huang] 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. Springer Science+Business Media New York, 2015 Cardiac hypertrophy nationallicence Sterile alpha motif and leucine zipper containing kinase nationallicence Mixed lineage kinase nationallicence Hsieh You-Liang Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan aut Tsai Ying-Lan Athletic Training and Health Department, National Taiwan Sport University, 333, Taoyuan, Taiwan aut Shibu Marthandam Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, ROC aut Su Chia-chi Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, ROC aut Chung Li-Chin Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy & Science, Tainan, Taiwan aut Pai Peiying Department of Dermatology, Taipei City Hospital, Taipei, Taiwan aut Kuo Chia-Hua Chinese Medicine Department, China Medical University Beigang Hospital, Yunlin, Taiwan aut Yeh Yu-Lan Department of pathology, Changhua Christian Hospital, Changhua, Taiwan aut Viswanadha Vijaya Department of Biotechnology, Bharathiar University, 641 046, Coimbatore, India aut Huang Chih-Yang Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 405/1-2(2015-07-01), 1-9 0300-8177 405:1-2<1 2015 405 11010 https://doi.org/10.1007/s11010-015-2389-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2389-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hsieh You-Liang Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan aut NATIONALLICENCE 700 1- Tsai Ying-Lan Athletic Training and Health Department, National Taiwan Sport University, 333, Taoyuan, Taiwan aut NATIONALLICENCE 700 1- Shibu Marthandam Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, ROC aut NATIONALLICENCE 700 1- Su Chia-chi Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, ROC aut NATIONALLICENCE 700 1- Chung Li-Chin Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy & Science, Tainan, Taiwan aut NATIONALLICENCE 700 1- Pai Peiying Department of Dermatology, Taipei City Hospital, Taipei, Taiwan aut NATIONALLICENCE 700 1- Kuo Chia-Hua Chinese Medicine Department, China Medical University Beigang Hospital, Yunlin, Taiwan aut NATIONALLICENCE 700 1- Yeh Yu-Lan Department of pathology, Changhua Christian Hospital, Changhua, Taiwan aut NATIONALLICENCE 700 1- Viswanadha Vijaya Department of Biotechnology, Bharathiar University, 641 046, Coimbatore, India aut NATIONALLICENCE 700 1- Huang Chih-Yang Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 405/1-2(2015-07-01), 1-9 0300-8177 405:1-2<1 2015 405 11010