Nitrosative stress-induced apoptosis through inhibition of NF-kappa B.

Journal Article (Journal Article)

Nitrosative stress produced by cytokines predisposes to apoptotic cell death. However, the molecular mechanism by which this occurs is not well understood. We have shown previously that nitric oxide (NO) regulates the activity of the anti-apoptotic transcription factor NF-kappaB. Here we demonstrate that the inhibition of NF-kappaB by NO sensitizes A549 and Jurkat T cells to tumor necrosis factor-alpha (TNFalpha)-induced apoptosis. The molecular basis of NF-kappaB inhibition is different in the two cell types. In A549 cells, NO functions at the nuclear level to inhibit NF-kappaB by S-nitrosylation. In Jurkat cells, NO inhibits the NF-kappaB activating pathway in the cytoplasm at a step proximal to the degradation of IkappaBalpha. The inhibition of NF-kappaB is reflected in the level of intracellular S-nitrosothiols, which are constitutively metabolized. These data suggest that NO can influence cell death by modulating NF-kappaB activity with the sites of inhibition being cell type-specific. The data also show that NO bioactivity regulates tumor necrosis factor-alpha signaling.

Full Text

Duke Authors

Cited Authors

  • Marshall, HE; Stamler, JS

Published Date

  • September 13, 2002

Published In

Volume / Issue

  • 277 / 37

Start / End Page

  • 34223 - 34228

PubMed ID

  • 12091382

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M201638200


  • eng

Conference Location

  • United States