Endogenous enzymes (NOX and ECSOD) regulate smoke-induced oxidative stress

Angela K. Tollefson, Rebecca E Deegan, Kiel T. Butterfield, Michael E. Nicks, Michael R. Weaver, Linda K. Remigio, Jessica Decsesznak, H. W. Chu, Donna L. Bratton, David W. Riches, Russell P. Bowler

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States and the incidence is increasing as the population ages. Cigarette smoking is the primary risk factor; however, only a minority of smokers develop the disease. Inhalation of cigarette smoke introduces an abundance of free radicals into the lungs, causing oxidative stress and inflammation. We hypothesized that after the initial burst of oxidative stress associated with cigarette smoke exposure, a sustained source of endogenous free radical production is modulated by the antioxidant enzyme extracellular superoxide dismutase (ECSOD) and the superoxide-generating complex NADPH oxidase (NOX). Primary mouse macrophages exposed to cigarette smoke extract exhibited increased oxidative stress as indicated by fluorogenic dyes and isoprostane concentration, which was suppressed in the presence of both a superoxide dismutase mimetic and a NOX inhibitor. Similarly, primary macrophages isolated from ECSOD-overexpressing mice or NOX-deficient mice showed reduced oxidative stress in response to cigarette smoke treatment. In addition, both reduced glutathione and cytokines (MIP2 and IFNγ) were increased in bronchoalveolar lavage fluid of wild-type mice exposed to cigarette smoke but not in ECSOD-overexpressing or NOX-deficient mice. These data suggest that the mechanisms underlying the host defense against cigarette smoke-induced oxidative damage and subsequent development of COPD may include endogenous oxidases and antioxidant enzymes.

Original languageEnglish (US)
Pages (from-to)1937-1946
Number of pages10
JournalFree Radical Biology and Medicine
Volume49
Issue number12
DOIs
StatePublished - Dec 15 2010

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Oxidative stress
NADPH Oxidase
Smoke
Tobacco Products
Superoxide Dismutase
Oxidative Stress
Enzymes
Pulmonary diseases
Macrophages
Chronic Obstructive Pulmonary Disease
Free Radicals
Antioxidants
Isoprostanes
Bronchoalveolar Lavage Fluid
Inhalation
Glutathione
Cause of Death
Oxidoreductases
Superoxides
Coloring Agents

Keywords

  • 4-HNE
  • Antioxidants
  • BALF
  • COPD
  • Cytokines
  • Extracellular superoxide dismutase
  • Free radicals
  • GSH
  • Lung
  • Macrophages
  • NADPH oxidase
  • Oxidative stress
  • ROS
  • Smoke

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Tollefson, A. K., Deegan, R. E., Butterfield, K. T., Nicks, M. E., Weaver, M. R., Remigio, L. K., ... Bowler, R. P. (2010). Endogenous enzymes (NOX and ECSOD) regulate smoke-induced oxidative stress. Free Radical Biology and Medicine, 49(12), 1937-1946. https://doi.org/10.1016/j.freeradbiomed.2010.09.022

Endogenous enzymes (NOX and ECSOD) regulate smoke-induced oxidative stress. / Tollefson, Angela K.; Deegan, Rebecca E; Butterfield, Kiel T.; Nicks, Michael E.; Weaver, Michael R.; Remigio, Linda K.; Decsesznak, Jessica; Chu, H. W.; Bratton, Donna L.; Riches, David W.; Bowler, Russell P.

In: Free Radical Biology and Medicine, Vol. 49, No. 12, 15.12.2010, p. 1937-1946.

Research output: Contribution to journalArticle

Tollefson, AK, Deegan, RE, Butterfield, KT, Nicks, ME, Weaver, MR, Remigio, LK, Decsesznak, J, Chu, HW, Bratton, DL, Riches, DW & Bowler, RP 2010, 'Endogenous enzymes (NOX and ECSOD) regulate smoke-induced oxidative stress', Free Radical Biology and Medicine, vol. 49, no. 12, pp. 1937-1946. https://doi.org/10.1016/j.freeradbiomed.2010.09.022
Tollefson, Angela K. ; Deegan, Rebecca E ; Butterfield, Kiel T. ; Nicks, Michael E. ; Weaver, Michael R. ; Remigio, Linda K. ; Decsesznak, Jessica ; Chu, H. W. ; Bratton, Donna L. ; Riches, David W. ; Bowler, Russell P. / Endogenous enzymes (NOX and ECSOD) regulate smoke-induced oxidative stress. In: Free Radical Biology and Medicine. 2010 ; Vol. 49, No. 12. pp. 1937-1946.
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