H(2)O(2)-induced O(2) production by a non-phagocytic NAD(P)H oxidase causes oxidant injury.

Published

Journal Article

Non-phagocytic NAD(P)H oxidases have been implicated as major sources of reactive oxygen species in blood vessels. These oxidases can be activated by cytokines, thereby generating O(2), which is subsequently converted to H(2)O(2) and other oxidant species. The oxidants, in turn, act as important second messengers in cell signaling cascades. We hypothesized that reactive oxygen species, themselves, can activate the non-phagocytic NAD(P)H oxidases in vascular cells to induce oxidant production and, consequently, cellular injury. The current report demonstrates that exogenous exposure of non-phagocytic cell types of vascular origin (smooth muscle cells and fibroblasts) to H(2)O(2) activates these cell types to produce O(2) via an NAD(P)H oxidase. The ensuing endogenous production of O(2) contributes significantly to vascular cell injury following exposure to H(2)O(2). These results suggest the existence of a feed-forward mechanism, whereby reactive oxygen species such as H(2)O(2) can activate NAD(P)H oxidases in non-phagocytic cells to produce additional oxidant species, thereby amplifying the vascular injury process. Moreover, these findings implicate the non-phagocytic NAD(P)H oxidase as a novel therapeutic target for the amelioration of the biological effects of chronic oxidant stress.

Full Text

Duke Authors

Cited Authors

  • Li, WG; Miller, FJ; Zhang, HJ; Spitz, DR; Oberley, LW; Weintraub, NL

Published Date

  • August 3, 2001

Published In

Volume / Issue

  • 276 / 31

Start / End Page

  • 29251 - 29256

PubMed ID

  • 11358965

Pubmed Central ID

  • 11358965

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M102124200

Language

  • eng

Conference Location

  • United States