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

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11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)31-37
Number of pages7
JournalChinese Journal of Physiology
Volume52
Issue number1
DOIs
Publication statusPublished - 2009 Jan 1

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

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