An apoptotic model for nitrosative stress.

Journal Article (Journal Article)

Nitric oxide overproduction has been implicated in the pathogenesis of many disorders, including artherosclerosis, neurodegenerative diseases, inflammatory and autoimmune diseases, and cancer. The common view holds that nitric oxide-induced cellular injury is caused by oxidative stress. This theory predicts that interactions between reactive nitrogen species and reactive oxygen species produce powerful oxidants that initiate cell death programs. Cytokine-treated murine macrophages are the prototype of this form of cellular injury. Here we report that generation of reactive nitrogen species upon lipopolysacharide/interferon-gamma stimulation of RAW 264.7 cells is largely divorced from production of reactive oxygen species, and that oxidative stress is not principally responsible for cell death (in this model). Rather, the death program is induced mainly by a nitrosative challenge, characterized by the accrual of nitrosylated proteins without a major alteration in cellular redox state. Moreover, interactions between reactive oxygen and nitrogen species may alter the balance between pathways that yield nitrite and nitrate, without impacting the level of S-nitrosylation or extent of cell death. Our results thus (1) provide new insights into NO-related metabolic pathways, (2) demonstrate that apoptotic injury can be caused by nitrosative mechanisms, and (3) establish a model for nitrosative stress in mammalian cells.

Full Text

Duke Authors

Cited Authors

  • Eu, JP; Liu, L; Zeng, M; Stamler, JS

Published Date

  • February 8, 2000

Published In

Volume / Issue

  • 39 / 5

Start / End Page

  • 1040 - 1047

PubMed ID

  • 10653649

Pubmed Central ID

  • 10653649

International Standard Serial Number (ISSN)

  • 0006-2960

Digital Object Identifier (DOI)

  • 10.1021/bi992046e


  • eng

Conference Location

  • United States