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Physiological Reviews, Vol. 82, No. 1, January 2002, pp. 47-95; 10.1152/physrev.00018.2001.
Copyright ©2002 by the American Physiological Society
Division of Immunochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
Dröge, Wulf
Free Radicals in the Physiological Control of Cell
Function. Physiol. Rev. 82: 47-95, 2002.
At high concentrations, free radicals and
radical-derived, nonradical reactive species are hazardous for
living organisms and damage all major cellular constituents. At
moderate concentrations, however, nitric oxide (NO), superoxide anion,
and related reactive oxygen species (ROS) play an important role as
regulatory mediators in signaling processes. Many of the
ROS-mediated responses actually protect the cells against oxidative
stress and reestablish "redox homeostasis." Higher organisms,
however, have evolved the use of NO and ROS also as signaling molecules
for other physiological functions. These include regulation of vascular
tone, monitoring of oxygen tension in the control of ventilation and
erythropoietin production, and signal transduction from membrane
receptors in various physiological processes. NO and ROS are typically
generated in these cases by tightly regulated enzymes such as NO
synthase (NOS) and NAD(P)H oxidase isoforms, respectively. In a given
signaling protein, oxidative attack induces either a loss of function,
a gain of function, or a switch to a different function. Excessive amounts of ROS may arise either from excessive stimulation of NAD(P)H
oxidases or from less well-regulated sources such as the mitochondrial electron-transport chain. In mitochondria, ROS are generated as undesirable side products of the oxidative energy metabolism. An excessive and/or sustained increase in ROS production has been implicated in the pathogenesis of cancer, diabetes mellitus, atherosclerosis, neurodegenerative diseases, rheumatoid arthritis, ischemia/reperfusion injury, obstructive sleep apnea, and other diseases. In addition, free radicals have been implicated in the mechanism of senescence. That the process of aging may result, at least
in part, from radical-mediated oxidative damage was proposed more
than 40 years ago by Harman (J Gerontol 11: 298-300,
1956). There is growing evidence that aging involves, in
addition, progressive changes in free radical-mediated regulatory
processes that result in altered gene expression.
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X. Xu, J. L. Page, J. A. Surtees, H. Liu, S. Lagedrost, Y. Lu, R. Bronson, E. Alani, A. Yu. Nikitin, and R. S. Weiss Broad Overexpression of Ribonucleotide Reductase Genes in Mice Specifically Induces Lung Neoplasms Cancer Res., April 15, 2008; 68(8): 2652 - 2660. [Abstract] [Full Text] [PDF]
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 A. V. Kuznetsov, J. Smigelskaite, C. Doblander, M. Janakiraman, M. Hermann, M. Wurm, S. F. Scheidl, R. Sucher, A. Deutschmann, and J. Troppmair Survival Signaling by C-RAF: Mitochondrial Reactive Oxygen Species and Ca2+ Are Critical Targets Mol. Cell. Biol., April 1, 2008; 28(7): 2304 - 2313. [Abstract] [Full Text] [PDF]
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E. Lorne, J. W. Zmijewski, X. Zhao, G. Liu, Y. Tsuruta, Y.-J. Park, H. Dupont, and E. Abraham Role of extracellular superoxide in neutrophil activation: interactions between xanthine oxidase and TLR4 induce proinflammatory cytokine production Am J Physiol Cell Physiol, April 1, 2008; 294(4): C985 - C993. [Abstract] [Full Text] [PDF]
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A. T. Baumer, H. ten Freyhaus, H. Sauer, M. Wartenberg, K. Kappert, P. Schnabel, C. Konkol, J. Hescheler, M. Vantler, and S. Rosenkranz Phosphatidylinositol 3-Kinase-dependent Membrane Recruitment of Rac-1 and p47phox Is Critical for {alpha}-Platelet-derived Growth Factor Receptor-induced Production of Reactive Oxygen Species J. Biol. Chem., March 21, 2008; 283(12): 7864 - 7876. [Abstract] [Full Text] [PDF]
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Z. Ungvari, C. Parrado-Fernandez, A. Csiszar, and R. de Cabo Mechanisms Underlying Caloric Restriction and Lifespan Regulation: Implications for Vascular Aging Circ. Res., March 14, 2008; 102(5): 519 - 528. [Abstract] [Full Text] [PDF]
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 A. Zamoner, K. P. Barreto, D. W. Filho, F. Sell, V. M. Woehl, F. C. R. Guma, R. Pessoa-Pureur, and F. R. M. B. Silva Propylthiouracil-induced congenital hypothyroidism upregulates vimentin phosphorylation and depletes antioxidant defenses in immature rat testis J. Mol. Endocrinol., March 1, 2008; 40(3): 125 - 135. [Abstract] [Full Text] [PDF]
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L. F. Ferreira and M. B. Reid Muscle-derived ROS and thiol regulation in muscle fatigue J Appl Physiol, March 1, 2008; 104(3): 853 - 860. [Abstract] [Full Text] [PDF]
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V. A. Campanucci, A. Krishnaswamy, and E. Cooper Mitochondrial Reactive Oxygen Species Inactivate Neuronal Nicotinic Acetylcholine Receptors and Induce Long-Term Depression of Fast Nicotinic Synaptic Transmission J. Neurosci., February 13, 2008; 28(7): 1733 - 1744. [Abstract] [Full Text] [PDF]
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 T. M. Paravicini and R. M. Touyz NADPH Oxidases, Reactive Oxygen Species, and Hypertension: Clinical implications and therapeutic possibilities Diabetes Care, February 1, 2008; 31(Supplement_2): S170 - S180. [Abstract] [Full Text] [PDF]
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 J. M. Mundt, S. S. Hah, R. A. Sumbad, V. Schramm, and P. T. Henderson Incorporation of extracellular 8-oxodG into DNA and RNA requires purine nucleoside phosphorylase in MCF-7 cells Nucleic Acids Res., January 17, 2008; 36(1): 228 - 236. [Abstract] [Full Text] [PDF]
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 V. Petrovic, B. Buzadzic, A. Korac, A. Vasilijevic, A. Jankovic, K. Micunovic, and B. Korac Antioxidative defence alterations in skeletal muscle during prolonged acclimation to cold: role of L-arginine/NO-producing pathway J. Exp. Biol., January 1, 2008; 211(1): 114 - 120. [Abstract] [Full Text] [PDF]
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 R. M. Mentzer Jr, M. S. Jahania, and R. D. Lasley Myocardial Protection Card. Surg. Adult, January 1, 2008; 3(2008): 443 - 464. [Full Text]
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Y. Duan, R. A. Gross, and S.-S. Sheu Ca2+-dependent generation of mitochondrial reactive oxygen species serves as a signal for poly(ADP-ribose) polymerase-1 activation during glutamate excitotoxicity J. Physiol., December 15, 2007; 585(3): 741 - 758. [Abstract] [Full Text] [PDF]
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J. Grillari, H. Katinger, and R. Voglauer Contributions of DNA interstrand cross-links to aging of cells and organisms Nucleic Acids Res., December 14, 2007; (2007) gkm1065v1. [Abstract] [Full Text] [PDF]
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A. R. Tupling, C. Vigna, R. J. Ford, S. C. Tsuchiya, D. A. Graham, S. G. Denniss, and J. W. E. Rush Effects of buthionine sulfoximine treatment on diaphragm contractility and SR Ca2+ pump function in rats J Appl Physiol, December 1, 2007; 103(6): 1921 - 1928. [Abstract] [Full Text] [PDF]
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Y. Lecarpentier Physiological role of free radicals in skeletal muscles J Appl Physiol, December 1, 2007; 103(6): 1917 - 1918. [Full Text] [PDF]
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Y.-T. Jia, W. Wei, B. Ma, Y. Xu, W.-J. Liu, Y. Wang, K.-Y. Lv, H.-T. Tang, D. Wei, and Z.-F. Xia Activation of p38 MAPK by Reactive Oxygen Species Is Essential in a Rat Model of Stress-Induced Gastric Mucosal Injury J. Immunol., December 1, 2007; 179(11): 7808 - 7819. [Abstract] [Full Text] [PDF]
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C. Tang, B. T. Ang, and S. Pervaiz Cancer stem cell: target for anti-cancer therapy FASEB J, December 1, 2007; 21(14): 3777 - 3785. [Abstract] [Full Text] [PDF]
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 A. L. Mundy, E. Haas, I. Bhattacharya, C. C. Widmer, M. Kretz, K. Baumann, and M. Barton Endothelin stimulates vascular hydroxyl radical formation: effect of obesity Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2007; 293(6): R2218 - R2224. [Abstract] [Full Text] [PDF]
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G. Ding, A. Zhang, S. Huang, X. Pan, G. Zhen, R. Chen, and T. Yang ANG II induces c-Jun NH2-terminal kinase activation and proliferation of human mesangial cells via redox-sensitive transactivation of the EGFR Am J Physiol Renal Physiol, December 1, 2007; 293(6): F1889 - F1897. [Abstract] [Full Text] [PDF]
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N. Tian, R. S. Moore, S. Braddy, R. A. Rose, J.-W. Gu, M. D. Hughson, and R. D. Manning Jr. Interactions between oxidative stress and inflammation in salt-sensitive hypertension Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3388 - H3395. [Abstract] [Full Text] [PDF]
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B. J. Hawkins, L. A. Solt, I. Chowdhury, A. S. Kazi, M. R. Abid, W. C. Aird, M. J. May, J. K. Foskett, and M. Madesh G Protein-Coupled Receptor Ca2+-Linked Mitochondrial Reactive Oxygen Species Are Essential for Endothelial/Leukocyte Adherence Mol. Cell. Biol., November 1, 2007; 27(21): 7582 - 7593. [Abstract] [Full Text] [PDF]
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