Activation of insulin-like growth factor II receptor induces mitochondrial-dependent apoptosis through Gαq and downstream calcineurin signaling in myocardial cells

Chun-Hsien Chu, Bor Show Tzang, Li Mien Chen, Chung Jung Liu, Fuu Jen Tsai, Chang Hai Tsai, James A. Lin, Wei Wen Kuo, Da Tian Bau, Chun Hsu Yao, Chih Yang Huang

研究成果: Article

48 引文 斯高帕斯(Scopus)

摘要

In previous studies, we have found that IGF-II and IGF-II receptor (IGF-IIR) dose dependently correlated with the progression of pathological hypertrophy after complete abdominal aorta ligation, which may play a critical role in angiotensin II-induced cardiomyocyte apoptosis. However, the detail mechanisms of IGF-IIR in the regulation of cell apoptosis in response to IGF-II remain unclear. By using IGF-IR short hairpin RNA to inhibit IGF-IR expression and using Leu27 IGF-II analog to activate specifically the IGF-IIR, we investigated the role of IGF-II/IGF-IIR activation and its downstream signaling. Our results revealed that IGF-II synergistically increased the cell apoptosis induced by suppressing of IGF-IR in neonatal rat ventricular myocytes. After binding of Leu27IGF-II, IGF-IIR became associated with α-q polypeptide, acted like a protein-coupled receptor to activate calcineurin, led to the translocation of Bad into mitochondria and release of cytochrome c into cytoplasm, and contributed to mitochondrial-dependent apoptosis in neonatal rat ventricular myocytes. Furthermore, inhibition of IGF-IIR, α-q polypeptide, or calcineurin by RNA interference could block the Leu27IGF-II-induced cell apoptosis. Together, this study provides a new insight into the effects of the IGF-IIR and its downstream signaling in myocardial apoptosis. Suppression of IGF-IIR signaling pathways may be a good strategy for both the protection against myocardial cell apoptosis and the prevention of heart failure progression.

原文English
頁(從 - 到)2723-2731
頁數9
期刊Endocrinology
150
發行號6
DOIs
出版狀態Published - 2009 六月 1

All Science Journal Classification (ASJC) codes

  • Endocrinology

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    Chu, C-H., Tzang, B. S., Chen, L. M., Liu, C. J., Tsai, F. J., Tsai, C. H., Lin, J. A., Kuo, W. W., Bau, D. T., Yao, C. H., & Huang, C. Y. (2009). Activation of insulin-like growth factor II receptor induces mitochondrial-dependent apoptosis through Gαq and downstream calcineurin signaling in myocardial cells. Endocrinology, 150(6), 2723-2731. https://doi.org/10.1210/en.2008-0975