Seo Miran, Nam Hyo-Jung, Kim So-Young, Juhnn Yong-Sung
Department of Biochemistry and Molecular Biology, Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Jongno-gu, Seoul 110-799, Republic of Korea.
Biochem Biophys Res Commun. 2009 Apr 3;381(2):153-8. doi: 10.1016/j.bbrc.2009.01.188. Epub 2009 Feb 20.
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.
抑制性异源三聚体GTP结合蛋白（Gi蛋白）通过偶联受体和效应器介导多种信号通路，以调节细胞增殖、分化和凋亡。然而，Gi蛋白在过氧化氢诱导的凋亡调节中的作用尚不清楚。因此，我们研究了Gi蛋白对过氧化氢诱导的H1299人肺癌细胞凋亡的影响及其潜在机制。组成型活性Gi1（Galphai1QL）、Gi2或Gi3的α亚基的稳定表达抑制了过氧化氢诱导的凋亡。Galphai1QL的表达上调了Bcl-2的表达，用小干扰RNA敲低Bcl-2消除了Galphai1QL的抗凋亡作用。Galphai1通过激活NF-κB诱导Bcl-2的转录，这是由NF-κB p50蛋白增加所致。我们得出结论，Galphai1通过p50介导的NF-κB激活上调Bcl-2的转录，从而抑制过氧化氢诱导的H1299肺癌细胞凋亡。
