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H2O2-induced O2⋅‒ Production by a Non-phagocytic NAD(P)H Oxidase Causes Oxidant Injury
Journal article   Open access   Peer reviewed

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 and Neal L. Weintraub
The Journal of biological chemistry, Vol.276(31), pp.29251-29256
05/17/2001
DOI: 10.1074/jbc.M102124200
PMCID: PMC3974124
PMID: 11358965
url
https://doi.org/10.1074/jbc.M102124200View
Published (Version of record) Open Access

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 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.

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