Inhibitory heterotrimeric GTP-binding proteins inhibit hydrogen peroxide-induced apoptosis by up-regulation of Bcl-2 via NF-{kappa}B in H1299 human lung cancer cells

Journal Article · Fri Apr 03 04:00:00 EDT 2009 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2009.01.188· OSTI ID:21255952

Seo, Mi Ran; Nam, Hyo-Jung; Kim, So-Young ^[1]; Juhnn, Yong-Sung ^[1]

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1. Department of Biochemistry and Molecular Biology, Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Jongno-gu, Seoul 110-799 (Korea, Republic of)

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 (G{alpha}i1QL), Gi2, or Gi3 inhibited hydrogen peroxide-induced apoptosis. The expression of G{alpha}i1QL up-regulated Bcl-2 expression, and the knockdown of Bcl-2 with siRNA abolished the anti-apoptotic effect of G{alpha}i1QL. G{alpha}i1 induced the transcription of Bcl-2 by activation of NF-{kappa}B, which resulted from an increase in NF-{kappa}B p50 protein. We conclude that G{alpha}i1 inhibits hydrogen peroxide-induced apoptosis of H1299 lung cancer cells by up-regulating the transcription of Bcl-2 through a p50-mediated NF-{kappa}B activation.

• OSTI ID: 21255952
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 381; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL PROLIFERATION
GENE REGULATION
GTP-ASES
HUMAN POPULATIONS
HYDROGEN PEROXIDE
LUNGS
NEOPLASMS
RECEPTORS
TRANSCRIPTION