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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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cAMP antagonizes ERK-dependent antiapoptotic action of insulin

  • Cui, Zhi Gang (Department of Medicine, School of Medicine and Institute of Medical Science, Jeju National University) ;
  • Hong, Na-Young (Department of Medicine, School of Medicine and Institute of Medical Science, Jeju National University) ;
  • Guan, Jian (Department of Medicine, School of Medicine and Institute of Medical Science, Jeju National University) ;
  • Kang, Hee-Kyoung (Department of Medicine, School of Medicine and Institute of Medical Science, Jeju National University) ;
  • Lee, Dae-Ho (Department of Medicine, School of Medicine and Institute of Medical Science, Jeju National University) ;
  • Lee, Young-Ki (Department of Medicine, School of Medicine and Institute of Medical Science, Jeju National University) ;
  • Park, Deok-Bae (Department of Medicine, School of Medicine and Institute of Medical Science, Jeju National University)
  • Received : 2010.11.29
  • Accepted : 2010.12.17
  • Published : 2011.03.31
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Abstract

Insulin has antiapoptotic activity in various cell types. However, the signaling pathways underlying the antiapoptotic activity of insulin is not yet known. This study was conducted to determine if cAMP affects the antiapoptotic activity of insulin and the activity of PI3K and ERK in CHO cells expressing human insulin receptors (CHO-IR). Insulin-stimulated ERK activity was completely suppressed by cAMP-elevating agents like as pertussis toxin (Ptx) and cholera toxin (Ctx) after 4 h treatment. Insulin-stimulated PKB/Akt activity was not affected at all. Ptx treatment together with insulin increased the number of apoptotic cells and the degree of DNA fragmentation. Ctx or 8-br-cAMP treatment also increased the number of apoptotic cells and stimulated the cleavage of caspase-3 and the hydrolysis of PARP. Taken together, cAMP antagonizes the antiapoptotic activity of insulin and the main target molecule of cAMP in this process is likely ERK, not PI3K-dependent PKB/Akt.

Keywords

References

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