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Review ArticleReview Article

NADPH Oxidase-Mediated Redox Signaling: Roles in Cellular Stress Response, Stress Tolerance, and Tissue Repair

Fan Jiang, Yun Zhang and Gregory J. Dusting
David R. Sibley, ASSOCIATE EDITOR
Pharmacological Reviews March 2011, 63 (1) 218-242; DOI: https://doi.org/10.1124/pr.110.002980
Fan Jiang
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, Shandong Province, China (F.J., Y.Z.); and O'Brien Institute (G.J.D.) and Department of Surgery (F.J., G.J.D.), University of Melbourne, Melbourne, Victoria, Australia
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Yun Zhang
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, Shandong Province, China (F.J., Y.Z.); and O'Brien Institute (G.J.D.) and Department of Surgery (F.J., G.J.D.), University of Melbourne, Melbourne, Victoria, Australia
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Gregory J. Dusting
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, Shandong Province, China (F.J., Y.Z.); and O'Brien Institute (G.J.D.) and Department of Surgery (F.J., G.J.D.), University of Melbourne, Melbourne, Victoria, Australia
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David R. Sibley
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, Shandong Province, China (F.J., Y.Z.); and O'Brien Institute (G.J.D.) and Department of Surgery (F.J., G.J.D.), University of Melbourne, Melbourne, Victoria, Australia
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Abstract

NADPH oxidase (Nox) has a dedicated function of generating reactive oxygen species (ROS). Accumulating evidence suggests that Nox has an important role in signal transduction in cellular stress responses. We have reviewed the current evidence showing that the Nox system can be activated by a collection of chemical, physical, and biological cellular stresses. In many circumstances, Nox activation fits to the cellular stress response paradigm, in that (1) the response can be initiated by various forms of cellular stresses; (2) Nox-derived ROS may activate mitogen-activated protein kinases (extracellular signal-regulated kinase, p38) and c-Jun NH2-terminal kinase, which are the core of the cell stress-response signaling network; and (3) Nox is involved in the development of stress cross-tolerance. Activation of the cell survival pathway by Nox may promote cell adaptation to stresses, whereas Nox may also convey signals toward apoptosis in irreversibly injured cells. At later stage after injury, Nox is involved in tissue repair by modulating cell proliferation, angiogenesis, and fibrosis. We suggest that Nox may have an integral role in cell stress responses and the subsequent tissue repair process. Understanding Nox-mediated redox signaling mechanisms may be of prominent significance at the crossroads of directing cellular responses to stress, aiming at either enhancing the stress resistance (in such situations as preventing ischemia-reperfusion injuries and accelerating wound healing) or sensitizing the stress-induced cytotoxicity for proliferative diseases such as cancer. Therefore, an optimal outcome of interventions on Nox will only be achieved when this is dealt with in a timely and disease-and stage-specific manner.

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  • This article is available online at http://pharmrev.aspetjournals.org.

    doi:10.1124/pr.110.002980.

  • © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 63 (1)
Pharmacological Reviews
Vol. 63, Issue 1
1 Mar 2011
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Review ArticleReview Article

NADPH Oxidase-Mediated Redox Signaling: Roles in Cellular Stress Response, Stress Tolerance, and Tissue Repair

Fan Jiang, Yun Zhang and Gregory J. Dusting
Pharmacological Reviews March 1, 2011, 63 (1) 218-242; DOI: https://doi.org/10.1124/pr.110.002980

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Review ArticleReview Article

NADPH Oxidase-Mediated Redox Signaling: Roles in Cellular Stress Response, Stress Tolerance, and Tissue Repair

Fan Jiang, Yun Zhang and Gregory J. Dusting
Pharmacological Reviews March 1, 2011, 63 (1) 218-242; DOI: https://doi.org/10.1124/pr.110.002980
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  • Article
    • Abstract
    • I. Introduction
    • II. NADPH Oxidase Is Activated by Various Cellular Stresses
    • III. Signal Output from NADPH Oxidase
    • IV. Cell Survival versus Apoptosis
    • V. Mechanisms of NADPH Oxidase Activation
    • VI. NADPH Oxidase and the Stress Response Signaling Paradigm
    • VII. NADPH Oxidase and Tissue Regeneration
    • VIII. Role of NADPH Oxidase-Mediated Stress Response in Vivo
    • IX. Concluding Remarks—NADPH Oxidase at the Crossroads
    • Authorship Contributions
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