p22(phox) is a critical component of the superoxide-generating NADH/NADPH oxidase system and regulates angiotensin II-induced hypertrophy in vascular smooth muscle cells

Masuko Ushio-Fukai, A. Maziar Zafari, Toshiki Fukui, Nobukazu Ishizaka, Kathy K. Griendling

Research output: Contribution to journalArticle

671 Citations (Scopus)

Abstract

Superoxide anion formation is vital to the microbicidal activity of phagocytes. Recently, however, there is accumulating evidence that it is also involved in cell growth in vascular smooth muscle cells (VSMCs). We have shown that the hypertrophic agent angiotensin II stimulates superoxide production by activating the membrane-bound NADH/NADPH oxidase and that inhibition of this oxidase attenuates vascular hypertrophy. However, the molecular identity of this oxidase in VSMCs is unknown. We have recently cloned the cytochrome b558 α-subunit, p22(phox) (one of the key electron transfer elements of the NADPH oxidase in phagocytes), from a rat VSMC cDNA library, but its role in VSMC oxidase activity remains unclarified. Here we report that the complete inhibition of p22(phox) mRNA expression by stable transfection of antisense p22(phox) cDNA into VSMCs results in a decrease in cytochrome b content, which is accompanied by a significant inhibition of angiotensin II-stimulated NADH/NADPH.dependent superoxide production, subsequent hydrogen peroxide production, and [3H]leucine incorporation. We provide the first evidence that p22(phox) is a critical component of superoxide-generating vascular NADH/NADPH oxidase and suggest a central role for this oxidase system in vascular hypertrophy.

Original languageEnglish (US)
Pages (from-to)23317-23321
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number38
DOIs
StatePublished - Jan 1 1996

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NADPH Oxidase
Vascular Smooth Muscle
Superoxides
Angiotensin II
NAD
Hypertrophy
Smooth Muscle Myocytes
Muscle
Cells
Oxidoreductases
Blood Vessels
Phagocytes
Cytochromes b
Cell growth
NADP
Gene Library
Leucine
Hydrogen Peroxide
Transfection
Rats

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

p22(phox) is a critical component of the superoxide-generating NADH/NADPH oxidase system and regulates angiotensin II-induced hypertrophy in vascular smooth muscle cells. / Ushio-Fukai, Masuko; Maziar Zafari, A.; Fukui, Toshiki; Ishizaka, Nobukazu; Griendling, Kathy K.

In: Journal of Biological Chemistry, Vol. 271, No. 38, 01.01.1996, p. 23317-23321.

Research output: Contribution to journalArticle

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