Activation of Insulin-Like Growth Factor II Receptor Induces Mitochondrial-Dependent Apoptosis through Gαq and Downstream Calcineurin Signaling in Myocardial Cells

• DOI: 10.1210/en.2008-0975
• Publication Date: 2008-12-19T01:44:24Z
• Authors: 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
• Keywords: 0301 basic medicine; Calcineurin; Myocardium; Cytochromes c; Apoptosis; Mitochondria, Heart; Receptor, IGF Type 2; Rats; 3. Good health; Rats, Sprague-Dawley; 03 medical and health sciences; Models, Animal; Animals; GTP-Binding Protein alpha Subunits, Gq-G11; RNA Interference; bcl-Associated Death Protein; Cells, Cultured; Signal Transduction

In previous studies, we have found that IGF-II and 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, detail mechanisms IGF-IIR regulation cell apoptosis response to remain unclear. By using IGF-IR short hairpin RNA inhibit expression Leu27 analog activate specifically IGF-IIR, investigated IGF-II/IGF-IIR activation its downstream signaling. Our results revealed synergistically increased induced by suppressing neonatal rat ventricular myocytes. After binding Leu27IGF-II, became associated alpha-q polypeptide, acted like protein-coupled calcineurin, led translocation Bad into mitochondria release cytochrome c cytoplasm, contributed mitochondrial-dependent Furthermore, inhibition or calcineurin interference could block Leu27IGF-II-induced Together, this study provides new insight effects signaling myocardial Suppression pathways be good strategy for both protection against prevention heart failure progression.