H2O2-induced O2.- Production by a Non-phagocytic NAD(P)H Oxidase Causes Oxidant Injury

Wei Gen Li, Francis J. Miller, Hannah J. Zhang, Douglas R. Spitz, Larry W. Oberley, Neal L. Weintraub

Research output: Contribution to journalArticle

222 Scopus citations

Abstract

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 O2.-, which is subsequently converted to H2O2 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 H2O2 activates these cell types to produce O2.- via an NAD(P)H oxidase. The ensuing endogenous production of O2.- contributes significantly to vascular cell injury following exposure to H2O 2. These results suggest the existence of a feed-for. ward mechanism, whereby reactive oxygen species such as H2O2 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.

Original languageEnglish (US)
Pages (from-to)29251-29256
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number31
DOIs
StatePublished - Aug 3 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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