ZAKβ antagonizes and ameliorates the cardiac hypertrophic and apoptotic effects induced by ZAKα |
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| Authors: | Chien‐Yao Fu Wei‐Wen Kuo Tsung‐Jung Ho Su‐Ying Wen Ling‐Chun Lin Yan‐Shen Tseng Hui‐Chuan Hung Vijaya Padma Viswanadha Chih‐Yang Huang |
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| Institution: | 1. Graduate Institute of Aging Medicine, China Medical University, Taichung, Taiwan;2. Orthopaedic Department, Armed Forces General Hospital, Taichung, Taiwan;3. Department of Emergency Medicine, China Medical University Hospital, Taichung, Taiwan;4. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan;5. School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan;6. Chinese Medicine Department, China Medical University Beigang Hospital, Taiwan;7. Department of Dermatology, Taipei City Hospital, Renai Branch, Taipei, Taiwan;8. Center for General Education, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan;9. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan;10. Department of Nursing, National Taichung University of Science and Technology, Taichung, Taiwan;11. Department of Biotechnology, Bharathiar University, Coimbatore, India;12. Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan;13. Department of Health and Nutrition Biotechnology, Asia University, Taichung, TaiwanJaw‐Ji Yang and Chih‐Yang Huang contributed equally to this paper. |
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| Abstract: | ZAK (sterile alpha motif and leucine zipper containing kinase AZK), a serine/threonine kinase with multiple biochemical functions, has been associated with various cell processes, including cell proliferation, cell differentiation, and cardiac hypertrophy. In our previous reports, we found that the activation of ZAKα signaling was critical for cardiac hypertrophy. In this study, we show that the expression of ZAKα activated apoptosis through both a FAS‐dependent pathway and a mitochondria‐dependent pathway by subsequently inducing caspase‐3. ZAKβ, an isoform of ZAKα, is dramatically expressed during cardiac hypertrophy and apoptosis. The interaction between ZAKα and ZAKβ was demonstrated here using immunoprecipitation. The results show that ZAKβ has the ability to diminish the expression level of ZAKα. These findings reveal an inherent regulatory role of ZAKβ to antagonize ZAKα and to subsequently downregulate the cardiac hypertrophy and apoptosis induced by ZAKα. |
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| Keywords: | cardiac apoptosis cardiac hypertrophy sterile alpha motif and leucine zipper containing kinase ZAKα ZAKβ |
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