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  • Title: Inhibitory heterotrimeric GTP-binding proteins inhibit hydrogen peroxide-induced apoptosis by up-regulation of Bcl-2 via NF-kappaB in H1299 human lung cancer cells.
    Author: Seo M, Nam HJ, Kim SY, Juhnn YS.
    Journal: Biochem Biophys Res Commun; 2009 Apr 03; 381(2):153-8. PubMed ID: 19233129.
    Abstract:
    Inhibitory heterotrimeric GTP-binding proteins (Gi proteins) mediate a variety of signaling pathways by coupling receptors and effectors to regulate cellular proliferation, differentiation, and apoptosis. However, the role of Gi proteins in the modulation of hydrogen peroxide-induced apoptosis is not clearly understood. Thus, we investigated the effect of Gi proteins on hydrogen peroxide-induced apoptosis and the underlying mechanisms in H1299 human lung cancer cells. The stable expression of constitutively active alpha subunits of Gi1 (Galphai1QL), Gi2, or Gi3 inhibited hydrogen peroxide-induced apoptosis. The expression of Galphai1QL up-regulated Bcl-2 expression, and the knockdown of Bcl-2 with siRNA abolished the anti-apoptotic effect of Galphai1QL. Galphai1 induced the transcription of Bcl-2 by activation of NF-kappaB, which resulted from an increase in NF-kappaB p50 protein. We conclude that Galphai1 inhibits hydrogen peroxide-induced apoptosis of H1299 lung cancer cells by up-regulating the transcription of Bcl-2 through a p50-mediated NF-kappaB activation.
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