PlumX Metrics
Embed PlumX Metrics

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

Endocrinology, ISSN: 0013-7227, Vol: 150, Issue: 6, Page: 2723-2731
2009
  • 55
    Citations
  • 0
    Usage
  • 15
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

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. Copyright © 2009 by The Endocrine Society.

Bibliographic Details

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

The Endocrine Society

Biochemistry, Genetics and Molecular Biology

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know