Tumour necrosis factor α activates a p22phox-based NADH oxidase in vascular smooth muscle

Gilles W. De Keulenaer, R. Wayne Alexander, Masuko Fukai, Nobukazu Ishizaka, Kathy K. Griendling

Research output: Contribution to journalArticle

259 Citations (Scopus)

Abstract

Increasing experimental evidence suggests that non-phagocytic cells express a potent superoxide (O2 -.)-producing NADH oxidase that might be related to the phagocytic NADPH oxidase. Here we show that the cytokine tumour necrosis factor α(TNF-α) activates, in a time- and dose-dependent manner, a O2 -.-producing NADH oxidase in cultured rat aortic smooth-muscle cells. Dose-response experiments for NADH showed an upward shift of the curve for TNF-α-treated cells, suggesting that TNF-α increased the amount of available enzyme. Using the anti-sense transfection technique, we further demonstrate that the molecular identity of this oxidase includes p22phox (the α subunit of cytochrome b558 and part of the electron transfer component of the phagocytic NADPH oxidase), which we recently cloned from a rat vascular smooth-muscle cell cDNA library. In addition, prolonged treatment with TNF-α increased p22phox mRNA expression without affecting p22phox mRNA stability, and only when transcriptional activity was intact. These findings identify a p22phox-containing NADH oxidase as a source for cytokine-induced free radical production in vascular smooth-muscle cells and clarify some of the mechanisms involved in the regulation of vascular oxidase activity.

Original languageEnglish (US)
Pages (from-to)653-657
Number of pages5
JournalBiochemical Journal
Volume329
Issue number3
StatePublished - Feb 1 1998
Externally publishedYes

Fingerprint

Vascular Smooth Muscle
Muscle
Tumor Necrosis Factor-alpha
Cells
Smooth Muscle Myocytes
NADPH Oxidase
Rats
Oxidoreductases
Cytokines
Messenger RNA
RNA Stability
Gene Library
Superoxides
NAD
Free Radicals
Transfection
Blood Vessels
Electrons
NADH oxidase
Enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

De Keulenaer, G. W., Alexander, R. W., Fukai, M., Ishizaka, N., & Griendling, K. K. (1998). Tumour necrosis factor α activates a p22phox-based NADH oxidase in vascular smooth muscle. Biochemical Journal, 329(3), 653-657.

Tumour necrosis factor α activates a p22phox-based NADH oxidase in vascular smooth muscle. / De Keulenaer, Gilles W.; Alexander, R. Wayne; Fukai, Masuko; Ishizaka, Nobukazu; Griendling, Kathy K.

In: Biochemical Journal, Vol. 329, No. 3, 01.02.1998, p. 653-657.

Research output: Contribution to journalArticle

De Keulenaer, GW, Alexander, RW, Fukai, M, Ishizaka, N & Griendling, KK 1998, 'Tumour necrosis factor α activates a p22phox-based NADH oxidase in vascular smooth muscle', Biochemical Journal, vol. 329, no. 3, pp. 653-657.
De Keulenaer GW, Alexander RW, Fukai M, Ishizaka N, Griendling KK. Tumour necrosis factor α activates a p22phox-based NADH oxidase in vascular smooth muscle. Biochemical Journal. 1998 Feb 1;329(3):653-657.
De Keulenaer, Gilles W. ; Alexander, R. Wayne ; Fukai, Masuko ; Ishizaka, Nobukazu ; Griendling, Kathy K. / Tumour necrosis factor α activates a p22phox-based NADH oxidase in vascular smooth muscle. In: Biochemical Journal. 1998 ; Vol. 329, No. 3. pp. 653-657.
@article{4de8a127e74c462ba8e6beeac7d43b5b,
title = "Tumour necrosis factor α activates a p22phox-based NADH oxidase in vascular smooth muscle",
abstract = "Increasing experimental evidence suggests that non-phagocytic cells express a potent superoxide (O2 -.)-producing NADH oxidase that might be related to the phagocytic NADPH oxidase. Here we show that the cytokine tumour necrosis factor α(TNF-α) activates, in a time- and dose-dependent manner, a O2 -.-producing NADH oxidase in cultured rat aortic smooth-muscle cells. Dose-response experiments for NADH showed an upward shift of the curve for TNF-α-treated cells, suggesting that TNF-α increased the amount of available enzyme. Using the anti-sense transfection technique, we further demonstrate that the molecular identity of this oxidase includes p22phox (the α subunit of cytochrome b558 and part of the electron transfer component of the phagocytic NADPH oxidase), which we recently cloned from a rat vascular smooth-muscle cell cDNA library. In addition, prolonged treatment with TNF-α increased p22phox mRNA expression without affecting p22phox mRNA stability, and only when transcriptional activity was intact. These findings identify a p22phox-containing NADH oxidase as a source for cytokine-induced free radical production in vascular smooth-muscle cells and clarify some of the mechanisms involved in the regulation of vascular oxidase activity.",
author = "{De Keulenaer}, {Gilles W.} and Alexander, {R. Wayne} and Masuko Fukai and Nobukazu Ishizaka and Griendling, {Kathy K.}",
year = "1998",
month = "2",
day = "1",
language = "English (US)",
volume = "329",
pages = "653--657",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "3",

}

TY - JOUR

T1 - Tumour necrosis factor α activates a p22phox-based NADH oxidase in vascular smooth muscle

AU - De Keulenaer, Gilles W.

AU - Alexander, R. Wayne

AU - Fukai, Masuko

AU - Ishizaka, Nobukazu

AU - Griendling, Kathy K.

PY - 1998/2/1

Y1 - 1998/2/1

N2 - Increasing experimental evidence suggests that non-phagocytic cells express a potent superoxide (O2 -.)-producing NADH oxidase that might be related to the phagocytic NADPH oxidase. Here we show that the cytokine tumour necrosis factor α(TNF-α) activates, in a time- and dose-dependent manner, a O2 -.-producing NADH oxidase in cultured rat aortic smooth-muscle cells. Dose-response experiments for NADH showed an upward shift of the curve for TNF-α-treated cells, suggesting that TNF-α increased the amount of available enzyme. Using the anti-sense transfection technique, we further demonstrate that the molecular identity of this oxidase includes p22phox (the α subunit of cytochrome b558 and part of the electron transfer component of the phagocytic NADPH oxidase), which we recently cloned from a rat vascular smooth-muscle cell cDNA library. In addition, prolonged treatment with TNF-α increased p22phox mRNA expression without affecting p22phox mRNA stability, and only when transcriptional activity was intact. These findings identify a p22phox-containing NADH oxidase as a source for cytokine-induced free radical production in vascular smooth-muscle cells and clarify some of the mechanisms involved in the regulation of vascular oxidase activity.

AB - Increasing experimental evidence suggests that non-phagocytic cells express a potent superoxide (O2 -.)-producing NADH oxidase that might be related to the phagocytic NADPH oxidase. Here we show that the cytokine tumour necrosis factor α(TNF-α) activates, in a time- and dose-dependent manner, a O2 -.-producing NADH oxidase in cultured rat aortic smooth-muscle cells. Dose-response experiments for NADH showed an upward shift of the curve for TNF-α-treated cells, suggesting that TNF-α increased the amount of available enzyme. Using the anti-sense transfection technique, we further demonstrate that the molecular identity of this oxidase includes p22phox (the α subunit of cytochrome b558 and part of the electron transfer component of the phagocytic NADPH oxidase), which we recently cloned from a rat vascular smooth-muscle cell cDNA library. In addition, prolonged treatment with TNF-α increased p22phox mRNA expression without affecting p22phox mRNA stability, and only when transcriptional activity was intact. These findings identify a p22phox-containing NADH oxidase as a source for cytokine-induced free radical production in vascular smooth-muscle cells and clarify some of the mechanisms involved in the regulation of vascular oxidase activity.

UR - http://www.scopus.com/inward/record.url?scp=0032007564&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032007564&partnerID=8YFLogxK

M3 - Article

VL - 329

SP - 653

EP - 657

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 3

ER -