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

研究成果: Article同行評審

11 引文 斯高帕斯(Scopus)

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.

原文English
頁(從 - 到)31-37
頁數7
期刊Chinese Journal of Physiology
52
發行號1
DOIs
出版狀態Published - 2009 一月 1

All Science Journal Classification (ASJC) codes

  • 生理學
  • 生理學(醫學)

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