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http://asiair.asia.edu.tw/ir/handle/310904400/8394
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| Title: | Activation of Insulin-Like Growth Factor II Receptor Induces Mitochondrial-Dependent Apoptosis through G alpha q and Downstream Calcineurin Signaling in Myocardial Cells |
| Authors: | Chu, CH (Chu, Chun-Hsien);Tzang, BS (Tzang, Bor-Show);Chen, LM (Chen, Li-Mien);Liu, CJ (Liu, Chung-Jung);Tsai, FJ (Tsai, Fuu-Jen);Tsai, CH (Tsai, Chang-Hai);Lin, JA (Lin, James A.);Kuo, WW (Kuo, Wei-Wen);Bau, DT (Bau, Da-Tian);Yao, CH (Yao, Chun-Hsu);Huang, CY (Huang, Chih-Yang) |
| Contributors: | 保健系 |
| Keywords: | MANNOSE 6-PHOSPHATE RECEPTOR;RAT CARDIAC MYOCYTES;HEART-FAILURE;CARDIOMYOBLAST APOPTOSIS;G-PROTEINS;IGF-II;CALCIUM;BINDING;STIMULATION;PATHWAY |
| Date: | 2009-06 |
| Issue Date: | 2010-03-26 10:46:22 (UTC+8) |
| Publisher: | Asia University |
| Abstract: | 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 alpha-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, alpha-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. (Endocrinology 150: 2723-2731, 2009) |
| Relation: | ENDOCRINOLOGY 150 (6): 2723-2731 |
| Appears in Collections: | [食品營養與保健生技學系] 期刊論文
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| 311.docx | | 0Kb | Unknown | 531 | View/Open | | 311.doc | | 39Kb | Microsoft Word | 1076 | View/Open |
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