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 Lee Weintraub

Research output: Contribution to journalArticle

213 Citations (Scopus)

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

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NADPH Oxidase
Oxidants
Wounds and Injuries
Reactive Oxygen Species
Vascular System Injuries
Blood Vessels
Cell signaling
Blood vessels
Second Messenger Systems
Fibroblasts
Muscle
Vascular Smooth Muscle
Oxidoreductases
Smooth Muscle Myocytes
Cells
Cytokines

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

H2O2-induced O2.- Production by a Non-phagocytic NAD(P)H Oxidase Causes Oxidant Injury. / Li, Wei Gen; Miller, Francis J.; Zhang, Hannah J.; Spitz, Douglas R.; Oberley, Larry W.; Weintraub, Neal Lee.

In: Journal of Biological Chemistry, Vol. 276, No. 31, 03.08.2001, p. 29251-29256.

Research output: Contribution to journalArticle

Li, Wei Gen ; Miller, Francis J. ; Zhang, Hannah J. ; Spitz, Douglas R. ; Oberley, Larry W. ; Weintraub, Neal Lee. / H2O2-induced O2.- Production by a Non-phagocytic NAD(P)H Oxidase Causes Oxidant Injury. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 31. pp. 29251-29256.
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