International Journal of Medical Sciences

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17 January 2019

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Int J Med Sci 2018; 15(13):1537-1546. doi:10.7150/ijms.24296

Research Paper

Tumorous imaginal disc 1 (TID1) inhibits isoproterenol-induced cardiac hypertrophy and apoptosis by regulating c-terminus of hsc70-interacting protein (CHIP) mediated degradation of Gαs

Chih-Chung Feng1, Po-Hsiang Liao2,3, Hsiang-I Tsai2, Shiu-Min Cheng4, Liang-Yo Yang5, Vijaya PadmaViswanadha6, Lung-Fa Pan7,8, Ray-Jade Chen9, Jeng-Fan Lo10✉*, Chih-Yang Huang2,3,11,12✉*

1. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
2. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
3. Medical Research Center For Exosomes and Mitochondria Related Diseases, China Medical University Hospital, Taichung, Taiwan
4. Department of Psychology, Asia University, Taichung, Taiwan
5. Department of Physiology, School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
6. Department of Biotechnology, Bharathiar University, Coimbatore-641 046, India
7. Cardiology Department of Taichung Armed Forced General Hospital, Taichung, Taiwan
8. Department of Medical Imaging and Radiological Sciences of Central Taiwan University of Science and Technology
9. Department of Surgery, School of Medicine, Taipei Medical University, Taipei, Taiwan
10. Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan
11. Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan
12. Department of Biological Science, Asia University, Taichung, Taiwan
*These authors contributed equally to this work.

Abstract

Dilated cardiomyopathy (DCM) is the most common form of non-ischemic cardiomyopathy. It is characterized by ventricular chamber dilation, and myocyte hypertrophy. Human tumorous imaginal disc 1 (Tid1), a chaperone protein and response to regulate number of signaling molecules in the mitochondria or cytosol. Tid1 also plays a major role in preventing DCM; however, the role of Tid1 in isoproterenol (ISO)-induced cardiac apoptosis and hypertrophy remains unclear. H9c2 cells were pretreated Tid1 before ISO-induced hypertrophy and apoptosis and then evaluated by IHC, TUNEL assay, IFC, Co-IP, and Western blot. From the IHC experiment, we found that Tid1 proteins were increased in tissues from different stages of human myocardial infarction. Using H9c2 cardiomyoblast cells we found that Tid1 was decreased by ISO treatment. However, over-expression of Tid1S suppressed NFATc3, BNP and calcineurin protein expression and inhibited NFATc3 nuclear translocation in ISO induced cardiomyoblast cells. On the other hand, Tid1S over-expression activated survival proteins p-AKTser473 and decreased caspase-3 and cytochrome c expression. We also found that overexpression of Tid1 enhanced CHIP expression, and induced CHIP to ubiquitinate Gαs, resulting in increased Gαs degradation. Our study showed that Gαs is a novel substrate of CHIP, and we also found that the Tid1-CHIP complex plays an essential role in inhibiting ISO induced cardiomyoblast hypertrophy and apoptosis.

Keywords: Tid1, H9c2, isoproterenol, hypertrophy, CHIP, Gαs

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How to cite this article:
Feng CC, Liao PH, Tsai HI, Cheng SM, Yang LY, PadmaViswanadha V, Pan LF, Chen RJ, Lo JF, Huang CY. Tumorous imaginal disc 1 (TID1) inhibits isoproterenol-induced cardiac hypertrophy and apoptosis by regulating c-terminus of hsc70-interacting protein (CHIP) mediated degradation of Gαs. Int J Med Sci 2018; 15(13):1537-1546. doi:10.7150/ijms.24296. Available from http://www.medsci.org/v15p1537.htm