There are growing evidences on the role of adaptive mechanisms of all cell types in pathological processes: atherosclerosis, ischemic attack, bacterial infections, etc. All kinds of these processes involve as main mechanism oxidative stress. Aerobic organisms use oxygen in processes that accidentally or deliberately generate aggressive species for the biologic components in the form of radicals. Radicals were looked initially as “harmful” molecules and this is true for large quantities but in small or even moderate amounts these molecules prove to have a physiological role. Reactive species are highly reactive and as a consequence are short living species. Their impact is supposed to be limited in the proximity area of their formation. Instead recent evidences indicate their implications in cellular signaling suggesting that individual chemical properties of reactive species make a difference in their biological role. This paper presents superoxide, nitric oxide and peroxide radical generation under cellular changing conditions, the adapting behavior of the enzymes that synthesize and remove them as well as some therapeutic target in superoxide related pathology.
Vijayvergiya, C., Beal, M.F., Buck, J. and Manfredi, G. (2003) Mutant Superoxide Dismutase 1 Forms Aggregates in the Brain Mitochondrial Matrix of Amyotrophic Lateral Sclerosis Mice. Journal of Neuroscience, 25, 2463-2470. http://dx.doi.org/10.1523/JNEUROSCI.4385-04.2005
Wei, L. and Dirksen, R.T. (2012) Mitochondrial Superoxide Flashes: From Discovery to New Controversies. The Journal of General Physiology, 139, 425-434. http://dx.doi.org/10.1085/jgp.201210790
Xu, S.P. and Touyz, R.M. (2006) Reactive Oxygen Species and Vascular Remodeling in Hypertension: Still Alive. Canadian Journal of Cardiology, 22, 947-951. http://dx.doi.org/10.1016/S0828-282X(06)70314-2
Paravicini, T.M. and Touyz, R.M. (2006) Redox Signaling in Hypertension. Cardiovascular Research, 71, 247-258. http://dx.doi.org/10.1016/j.cardiores.2006.05.001
Lunderg, J.O. and Weitzber, E. (2005) NO Generation from Nitrite and Its Role in Vascular Control. Arteriosclerosis, Thrombosis, and Vascular Biology, 25, 915-922. http://dx.doi.org/10.1161/01.ATV.0000161048.72004.c2
van Faassen, E.E., et al. (2009) Nitrite as Regulator of Hypoxic Signaling in Mammalian Physiology. Medicinal Research Reviews, 29, 683-741. http://dx.doi.org/10.1002/med.20151
Heinrich, P., Löffler, G. and Petrides, P.E. (2006) Biochemie und Pathobiochemie. 123.
Abu-Soud, H.M. and Stuehr, D.J. (1993) Nitric Oxide Synthases Reveal a Role for Calmodulin in Controlling Electron Transfer. Proceedings of the National Academy of Sciences of the United States of America, 90, 10769-10772. http://dx.doi.org/10.1073/pnas.90.22.10769
van Hinsbergh, V.W.M. (2001) NO or H2O2 for Endothelium-Dependent Vasorelaxation. Tetrahidrobiopterin Makes the Differences. Arteriosclerosis, Thrombosis, and Vascular Biology, 21, 719-772. http://dx.doi.org/10.1161/01.ATV.21.5.719
Tojo, T., Ushio-Fukai, M., Yamaoka-Tojo, M., Ikeda, S., Patrushev, N. and Alexander, R.W. (2005) Role of gp91phox (Nox2)-Containing NAD(P)H Oxidase in Angiogenesis in Response to Hindlimb Ischemia. Circulation, 111, 2347-2355. http://dx.doi.org/10.1161/01.CIR.0000164261.62586.14
Raad, H., Paclet, M.-H., Boussetta, T., Kroviarski, Y., Morel, F., Quinn, M.T., Gougerot-Pocidalo, M.-A., Dang, P.M.-C. and El-Benna, J. (2009) Regulation of the Phagocyte NADPH Oxidase Activity: Phosphorylation of gp91phox/ NOX2 by Protein Kinase C Enhances Its Diaphorase Activity and Binding to Rac2. FASEB Journal, 23, 1011-1022. http://dx.doi.org/10.1096/fj.08-114553
Metzler, D.E. (2001) Biochemistry: The Chemical Reaction of Living Cells. Elsevier Academic Press.
Misra, H.P. and Fridovici, I. (1972) The Generation of Superoxide Radical during the Autoxidation of Hemoglobin. The Journal of Biological Chemistry, 247, 6960-6962.
Balagopalakrishna, C., Manoharan, P.T., Abugo, O.O. and Rifkind, J.M. (1996) Production of Superoxide from Hemoglobin-Bound Oxygen under Hypoxic Condition. Biochemistry, 35, 6393-6398. http://dx.doi.org/10.1021/bi952875+
Lang, D., Kredan, M.B., Moat, S.J., et al. (2000) Homocysteine-Induced Inhibition of Endothelium-Dependent Relaxation in Rabbit Aorta: Role for Superoxide Anions. Arteriosclerosis, Thrombosis, and Vascular Biology, 20, 422-427. http://dx.doi.org/10.1161/01.ATV.20.2.422
Pacher, P., Beckman, J.S. and Liaudet, L. (2007) Nitric Oxide and Peroxynitrite in Health and Disease. Physiological Reviews, 87, 315-424. http://dx.doi.org/10.1152/physrev.00029.2006
Sawyer, D.T. and Valentine, J. (1981) How Super Is Superoxide? Accounts of Chemical Research, 14, 393-400. http://dx.doi.org/10.1021/ar00072a005
Bhagavan, N.V. (2002) Medical Biochemistry. Harcourt/Academic Press.
Agullo, L. (2007) Ciclic GMP Advances.
Guzy, R.D. and Schumacker, P.T. (2006) Oxygen Sensing by Mitochondria at Complex III: The Paradox of Increased Reactive Oxygen Species during Hypoxia. Experimental Physiology, 91, 807-819. http://dx.doi.org/10.1113/expphysiol.2006.033506
Powers, S.K., Talbert, E.E. and Adhihetty, P.J. (2011) Reactive Oxygen and Nitrogen Species as Intracellular Signals in Skeletal Muscle. Journal of Physiology, 589, 2129-2138. http://dx.doi.org/10.1113/jphysiol.2010.201327
Stroes, E., Hijmering, M., van Zandvoort, M., Wever, R., Rabelink, T. and van Faassen, E. (1998) Origin of Superoxide Production by Endothelial Nitric Oxide Synthase. FEBS Letters, 438, 161-164. http://dx.doi.org/10.1016/S0014-5793(98)01292-7
Stroes, E., Rabelink, T. and van Faassen, E. (2002) Vascular Protection: Molecular Mechanisms, Novel Therapeutic Principles and Clinical Applications.
Denicola, A., Souza, J.M. and Radi, R. (1998) Diffusion of Peroxinitrite across Erythrocytes Membrane. Proceedings of the National Academy of Sciences of the United States of America, 95, 3566-3571. http://dx.doi.org/10.1073/pnas.95.7.3566
Miller, A.F. (2004) Superoxide Dismutases: Active Sites that Save, but a Protein that Kills. Current Opinion in Chemical Biology, 8, 162-168. http://dx.doi.org/10.1016/j.cbpa.2004.02.011
Miller, A.F. (2003) Superoxide Processing. In: Que Jr., L. and Tolman, W., Eds., Coordination Chemistry in the Biosphere and Geosphere, Pergamon, Oxford, Amsterdam, New York and Tokyo, 479-506.
Bull, C. and Fee, J.A. (1985) Steady-State Kinetic Studies of Superoxide Dismutases: Properties of the Iron Containing Protein from Escherichia coli. Journal of American Chemical Society, 107, 3295-3304. http://dx.doi.org/10.1021/ja00297a040
Miller, A.F., Padmakumar, K., Sorkin, D.L., Karapetian, A. and Vance, C.K. (2003) Proton-Coupled Electron Transfer in Fe-Superoxide Dismutase and Mn-Superoxide Dismutase. Journal of Inorganic Biochemistry, 93, 71-83. http://dx.doi.org/10.1016/S0162-0134(02)00621-9
Han, W.G., Lovell, T. and Noodleman, L. (2003) Coupled Redox Potentials in Manganese and Iron Superoxide Dismutases from Reaction Kinetics and Density Functional/Electrostatics Calculations. Inorganic Biochemistry, 41, 205-218. http://dx.doi.org/10.1021/ic010355z
Immenschuh, S. and Baumgart-Vogt, E. (2005) Peroxiredoxins, Oxidative Stress, and Cell Proliferation. Antioxidants & Redox Signaling, 7, 768-777. http://dx.doi.org/10.1089/ars.2005.7.768
James R Stone Lab-Projects. www.vascularpath.org
Paravicini, T.M., Chrissobolis, S., Drummond, G.R. and Sobey, C.G. (2004) Increased NAD(P)H-Oxidase Activity and Nox4 Expression during Chronic Hypertension Is Associated with Enhanced Cerebral Vasodilatation to NAD(P)H in Vivo. Stroke, 35, 584-589.
Filip, C., Albu, E., Zamosteanu, N., Jaba Irina, M., Silion, M., Jerca, L., Gheorghita, N. and Costel, M.O. (2010) Hyper-homocysteinemia’s Effect on Antioxidant Capacity on Rats. Central European Journal of Medicine, 5, 620-626. http://dx.doi.org/10.2478/s11536-010-0032-7
Lebovitz, R.M., Zhang, H., Vogel, H., Cartwright Jr., J., Dionne, L., Lu, N., Huang, S. and Matzuk, M.M. (1996) Neurodegeneration, Myocardial Injury, and Perinatal Death in Mitochondrial Superoxide Dismutase-Deficient Mice. Proceedings of the National Academy of Sciences of the United States of America, 93, 9782-9787. http://dx.doi.org/10.1073/pnas.93.18.9782
Duttaroy, A., Paul, A., Kundu, M. and Belton, A. (2003) A Sod2 Null Mutation Confers Severely Reduced Adult Life Span in Drosophila. Genetics, 165, 2295-2299.
Kirby, K., Hu, J., Hilliker, A.J. and Phillips, J.P. (2002) RNA Interference-Mediated Silencing of Sod2 in Drosophila Leads to Early Adult-Onset Mortality and Elevated Endogenous Oxidative Stress. Proceedings of the National Academy of Sciences of the United States of America, 99, 16162-16167. http://dx.doi.org/10.1073/pnas.252342899
Yamakura, F. and Kawasaki, H. (2010) Post-Translational Modifications of Superoxide Dismutase. Biochimica et Biophysica Acta, 1804, 318-325. http://dx.doi.org/10.1016/j.bbapap.2009.10.010
Fattmen, C.L., Schaefer, L.M. and Oury, T.D. (2003) Extracellular Superoxide Dismutase in Biology and Medicine. Free Radical Biology & Medicine, 35, 236-256. http://dx.doi.org/10.1016/S0891-5849(03)00275-2
Oury, T.D., Day, B.J. and Crapo, J.D. (1996) Extracellular Superoxide Dismutase in Vessels and Airways of Humans and Baboons. Free Radical Biology & Medicine, 20, 957-965. http://dx.doi.org/10.1016/0891-5849(95)02222-8
Stralin, P., Karlsson, K., Johansson, B.O. and Marklund, S.L. (1995) The Interstitium of the Human Arterial Wall Contains very Large Amounts of Extracellular Superoxide Dismutase. Arteriosclerosis, Thrombosis, and Vascular Biology, 15, 2032-2036. http://dx.doi.org/10.1161/01.ATV.15.11.2032
Culotta, V.C., Yang, M. and O’Halloran, T.V. (2006) Activation of Superoxide Dismutases: Putting the Metal to the Pedal. Biochimica et Biophysica Acta, 1763, 747-758.
Macmillan-Crow, L.A. and Cruthirds, D.L. (2001) Invited Review: Manganese Superoxide Dismutase in Disease. Free Radical Research, 34, 325-336. http://dx.doi.org/10.1080/10715760100300281
Sandstrom, J., Karlsson, K., Edlund, T. and Marklund, S.L. (1993) Heparin-Affinity Patterns and Composition of Extracellular Superoxide Dismutase in Human Plasma and Tissues. Biochemical Journal, 294, 853-857.
Bowler, R.P., Nicks, M., Olsen, D.A., Thogersen, I.B., Valnickova, Z., Hojrup, P., Franzusoff, A., Enghild, J.J. and Crapo, J.D. (2002) Furinproteolytically Processes the Heparin-Binding Region of Extracellular Superoxide Dismutase. Journal of Biological Chemistry, 277, 16505-16511. http://dx.doi.org/10.1074/jbc.M105409200
Gongora, M.C., Qin, Z., Laude, K., Kim, H.W., McCann, L., Folz, J.R., Dikalov, S., Fukai, T. and Harrison, D.G. (2006) Role of Extracellular Superoxide Dismutase in Hypertension. Hypertension, 48, 473-481. http://dx.doi.org/10.1161/01.HYP.0000235682.47673.ab
Lob, H.E., Marvar, P.J., Guzik, T.J., Sharma, S., McCann, L.A., Weyand, C., Gordon, F.J. and Harrison, D.G. (2010) Induction of Hypertension and Peripheral Inflammation by Reduction of Extracellular Superoxide Dismutase in the Central Nervous System. Hypertension, 55, 277-283. http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.142646
Sentman, M.L., Brannstrom, T., Westerlund, S., Laukkanen, M.O., Yla-Herttuala, S., Basu, S. and Marklund, S.L. (2001) Extracellular Superoxide Dismutase Deficiency and Atherosclerosis in Mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 21, 1477-1482. http://dx.doi.org/10.1161/hq0901.094248
Adachi, T., Ohta, H., Hirano, K., Hayashi, K. and Marklund, S.L. (1991) Non-Enzymic Glycation of Human Extracellular Superoxide Dismutase. Biochemical Journal, 279, 263-267.
Loscalzo, J. (1996) The Oxidant Stress of Hyperhomocyst(e)inemia. Journal of Clinical Investigation, 98, 5-7. http://dx.doi.org/10.1172/JCI118776
Yamamoto, M., Hara, H. and Adachi, T. (2000) Effects of Homocysteine on the Binding of Extracellular Superoxide Dismutase to the Endothelial Cell Surface. FEBS Letters, 486, 159-162. http://dx.doi.org/10.1016/S0014-5793(00)02260-2
Nonaka, H., Tsujino, T., Watari, Y., Emoto, N. and Yokoyama, M. (2001) Taurine Prevents the Decrease in Expression and Secretion of Extracellular Superoxide Dismutase Induced by Homocysteine: Amelioration of Homocysteine-Induced Endoplasmic Reticulum Stress by Taurine. Circulation, 104, 1165-1170. http://dx.doi.org/10.1161/hc3601.093976
Truong, T.H. and Carroll, K.S. (2013) Redox Regulation of Protein Kinases. Critical Reviews in Biochemistry and Molecular Biology, 48, 332-356.
Martindale, J.L. and Holbrook, N.J. (2002) Cellular Response to Oxidative Stress: Signaling for Suicide and Survival. Journal of Cellular Physiology, 192, 1-15. http://dx.doi.org/10.1002/jcp.10119
Dong, C., Davis, R.J. and Flavell, R.A. (2002) MAP Kinases in the Immune Response. Annual Review of Immunology, 20, 55-72. http://dx.doi.org/10.1146/annurev.immunol.20.091301.131133
Bahorun, T., Soobratte, M.A., Luximon-Ramma, V. and Aruoma, O.I. (2006) Free Radicals and Antioxidants in Cardiovascular Health and Disease. Internet Journal of Medical Update, 1, 25-40.
Novo, E. and Parola, M. (2008) Redox Mechanisms in Hepatic Chronic Wound Healing and Fibrogenesis. Fibrogenesis & Tissue Repair, 1, 5.
Chen, Z., Gibson, T.B., Robinson, F., Silvestro, L., Pearson, G., Xu, B., Wright, A., Vanderbilt, C. and Cobb, M.H. (2001) MAP Kinases. Chemical Reviews, 101, 2449-2476. http://dx.doi.org/10.1021/cr000241p
Powers, S.K., Duarte, J., Kavazis, A.N. and Talbert, E.E. (2010) Reactive Oxygen Species Are Signalling Molecules for Skeletal Muscle Adaptation. Experimental Physiology, 95, 1-9. http://dx.doi.org/10.1113/expphysiol.2009.050526
Droge, W. (2002) Free Radicals in the Physiological Control of Cell Function. Physiological Reviews, 82, 47-95.
Yin, M., Wheeler, M., Connor, H., Zhong, Z., Bunzendahl, H., Dikalova, A., Samulski, R., Schoonhoven, R., Mason, R., Swenberg, J. and Thurman, R. (2001) Cu/Zn-Superoxide Dismutase Gene Attenuates Ischemia-Reperfusion Injury in the Rat Kidney. Journal of the American Society of Nephrology, 12, 2691-2700.
Urushitani, M., Ezzi, S.A. and Julien, J.P. (2007) Therapeutic Effects of Immunization with Mutant Superoxide Dismutase in Mice Models of Amyotrophic Lateral Sclerosis. Proceedings of the National Academy of Sciences of the United States of America, 104, 2495-2500. http://dx.doi.org/10.1073/pnas.0606201104
Fukushima, S., Coppen, S., Varela-Carver, A., Brindley, G., Yamahara, K., Sarathchandra, P., Yacoub, M.H. and Suzuki, K. (2006) Enhanced Efficiency of Superoxide Dismutase-Induced Cardioprotection by Retrograde Intracoronary Administration. Cardiovascular Research, 69, 459-465. http://dx.doi.org/10.1016/j.cardiores.2005.10.008
Moukarbel, G.V., Ayoub, C.M. and Abchee, A.B. (2004) Pharmacological Therapy for Myocardial Reperfusion Injury. Current Opinion in Pharmacology, 4, 147-153. http://dx.doi.org/10.1016/j.coph.2003.10.012
Nikolaos, G., Frangogiannis, C., Smith, W. and Entman, M.L. (2002) The Inflammatory Response in Myocardial Infarction. Cardiovascular Research, 53, 31-47. http://dx.doi.org/10.1016/S0008-6363(01)00434-5
Barber, S.C. and Shaw, P.J. (2010) Oxidative Stress in ALS: Key Role in Motor Neuron Injury and Therapeutic Target. Free Radical Biology & Medicine, 48, 629-641. http://dx.doi.org/10.1016/j.freeradbiomed.2009.11.018