Enhancement of AG1024-Induced H9c2 Cardiomyoblast Cell Apoptosis via the Interaction of IGF2R with Gα Proteins and Its Downstream PKA and PLC-β Modulators by IGF-Ⅱ

Chun-Hsien Chu ； Chih-Yang Huang ； Ming-Chin Lu ； James A. Lin ； Fuu-Jen Tsai ； Chang-Hai Tsai ； Chia-Yih Chu ； Wu-Hsien Kuo ； Li-Mien Chen ； Ling-Yun Chen

《The Chinese Journal of Physiology》 52卷1期 (2009/02) Pp. 31-37

https://doi.org/10.4077/CJP.2009.AMH004

並列摘要

Our previous studies found that insulin-like growth factor-I receptor (IGF1R) signaling blockade caused cardiac hypertrophy, and that apoptosis is required for upregulating the IGF-Ⅱ and the IGF-Ⅱ mannose 6-phosphate receptor (IGF2R) gene. However, the role of IGF-Ⅱ in the regulation of cell apoptosis through IGF2R is little known. In this study, we hypothesized that IGF-Ⅱ may induce cell apoptosis through IGF2R but is dependent on IGF1R activity. Western blots and TUNEL assay revealed that in the presence of IGF1R, exogenous IGF-Ⅱ acts, like IGF-Ⅰ, would increase phospho-Akt through IGF1R, but does not affect the caspase 3 activation and apoptotic induction in H9c2 cardiomyoblast cells. Conversely, AG1024, an inhibitor of IGF1R activity, causes cell apoptosis, and the treatment with IGF-Ⅱ further enhances this process, implying that it occurs through IGF2R. Moreover, immunoprecipitation assay revealed that treatment with IGF-Ⅱ could enhance the interaction of IGF2R with Gαi and Gαq but reduce its binding with Gαs, resulting in the reduction of phospho-PKA and the activation of PLC-β. Taken together, these data provide new insight into the dual role of IGF-Ⅱ in the control of IGF1R dependent cell apoptosis and involved activation of IGF2R signaling. Improving IGF1R activity and suppressing IGF2R may be a good strategy to prevent the progression of heart disease with cardiomyocyte apoptosis.

並列關鍵字

IGF-Ⅱ ； apoptosis ； Gα ； IGF2R

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