Complexity of free radical Metabolism in human Erythrocytes
The auto-oxidation of oxyhaemoglobin to methaemoglobin generating superoxide anion radical (O2.-) represents the main source of free radicals in the erythro-cytes. Hydrogen peroxide is produced by O2.- dismutation or originates from the circulation. Human erythrocytes are also exposed to the prooxidative actions of nitric oxide (NO) from circulation. Free radicals that may induce reactions with direct dangerous consequences to erythrocytes are also preceded by the reaction of O2.- and NO producing peroxynitrite. In physiological settings, erythrocytes show a self-sustaining activity of antioxidative defence (AD) enzymes, such as: superoxide dismutase (SOD, EC 1.11.16), catalase (CAT, EC 220.127.116.11), glutathione peroxidase (GSHPx, EC 18.104.22.168) and glutathione reductase (GR, EC 22.214.171.124), as well as low molecular weight antioxidants: glutathione and vitamins E and C. Their coordinate actions protect the erythrocyte's bio-macromolecules from free radical-mediated damage. Since there is no de novo synthesis of AD enzymes in mature erythrocytes, their defence capacity is limited. Free radicals influence antioxidative enzymes capacities and relative share of particular components in the whole antioxidative system. Therefore, by measuring changes in the activity of individual AD components, as well as their interrelations by statistical canonical discriminant methods, valuable data about the complexity, overall relations and coordinated actions in the AD system in erythrocytes and its relevance for systemic effects can be acquired.
Rifkind JM, Nagababu E, Ramasamy S, Ravi LB. Hemo-globin redox reactions and oxidative stress. Redox Rep 2003; 8 (5): 234-7.
Winterbourn CC. Haemoglobin oxidation and free radical production in the red cell. Biomed Biochim Acta 1983; 42 (11-12): S134-8.
Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev 1979; 59 (3): 527-605.
Spasić MB. Antioxidative defence in mammals - A review. Jugoslov Med Biohem 1993; 12: 1-9.
Guemouri L, Artur Y, Herbeth B, Jeandel C, Cuny G, Siest G. Biological variability of superoxide dismutase, glutat-hione peroxidase, and catalase in blood. Clin Chem 1991; 37 (11): 1932-7.
Nikolić M, Vranić D, Spirić A, Batas V, Nikolić-Kokić A, Radetić P, et al. Could cholesterol bound to haemoglobin be a missing link for the occasional inverse relationship between superoxide dismutase and glutathione peroxidase activities? BBRC 2006; 348: 265-70.
Nikolić M, Nikolić-Kokić A, Stanić D, Blagojević DP, Vranić D, Jones D, Niketić V, Spasić MB. Does chole-sterol bound to haemoglobin affects the antioxidative enzyme defence system in human erythrocytes? J Serb Chem Soc 2007; 72: (4): 339-45.
Kasimanickam R, Kasimanickam V, Thatcher CD, Nebel RL, Cassell BG. Relations among lipid peroxidation, glutathione peroxidation, glutathione peroxidase, super-oxide dismutase, sperm parameters, and competitive index in dairy bulls. Theriogenology 2007; 67 (5): 1004-12.
Nikolić-Kokić A, Stević Z, Blagojević D, Davidović B, Jones DR, Spasić MB. Alterations in anti-oxidative defence enzymes in erythrocytes from sporadic amyo-trophic lateral sclerosis (SALS) and familial ALS patients. Clin Chem Lab Med 2006; 44 (5): 589-93.
Halliwell B, Gutteridge JMC. In: Free Radicals in Biology and Medicine, Fourth edition. New York, Oxford University Press Inc., 2007.
Blagojević D. Antioxidant systems in supporting environmental and programmed adaptations to low temperatures. Cryo Letters 2007; 28 (3): 137-50.
Blagojević D, Buzadžić B, Korać B, Saičić ZS, Radojičić R, Spasić MB, Petrović VM. Seasonal changes in the anti-oxidative defence in ground squirrels (Citellus citellus): possible role of GSH-Px. J Environ Pathol Toxicol Oncol 1998; 17 (3-4): 241-50.
Spasojević I. Electron paramagnetic resonance - A powerful tool of medical biochemistry in discovering mechanisms of disease and treatment prospects. Journal of Medical Biochemistry 2010; 29: 175-188.
Bunn HF. Pathophysiology of the anemias. In: Wilson JD, Braunwald E, Isselbacher KJ, editors. Harrison's Principle of Internal Medicine. New York: McGraw-Hill Inc; 1991; 1514-8.
Johnson RM, Goyette Jr G, Ravindranath Y, Ho YS. Hemoglobin autoxidation and regulation of endogenous H2O2 levels in erythrocytes. Free Radic Biol Med 2005; 39: 1407-17.
Chakraborty D, Bhattacharyya M. Antioxidant defense status of red blood cells of patients with beta-thalassemia and Ebeta-thalassemia. Clin Chim Acta 2001; 305: 123-9.
Tesoriere L, D'Arpa D, Butera, D, Allegra M, Renda D, Maggio A, Bongiorno A, Livrea MA. Oral supplements of vitamin E improve measures of oxidative stress in plasma and reduce oxidative damage to LDL and erythrocytes in beta-thalassemia intermedia patients. Free Radic Res 2001; 34: 529-40.
Padmaja S, Squadrito GL, Pryor WA. Inactivation of glutathione peroxidase by peroxynitrite. Arch Biochem Biophys 1998; 349: 1-6.
Mavelli I, Ciriolo MR, Rotilio G. Multiple electrophoretic variants of Cu, Zn superoxide dismutase as expression of the enzyme aging. Effects of H2O2, ascorbate and metal ions. Biochem Biophys Res Commun 1983; 117 (3): 677-81.
Hodgson EK, Fridovich I. The interaction of bovine erythrocyte superoxide dismutase with hydrogen peroxide: chemiluminescence and peroxidation. Biochemistry 1975; 14 (24): 5299-303.
Uchida K, Kawakishi S. Identification of oxidized histidine generated at the active site of Cu, Zn-superoxide dismutase exposed to H2O2. Selective generation of 2-oxo-histidine at the histidine 118. J Biol Chem 1994 28; 269 (4): 2405-10.
Yim MB, Chock PB, Stadtman ER. Copper, zinc super-oxide dismutase catalyzes hydroxyl radical production from hydrogen peroxide. Proc Natl Acad Sci USA 1990; 87 (13): 5006-10.
Jewett SL, Olmsted HK, Marach JA, Rojas F, Silva K. Anion protection of CuZnSOD during peroxidative activity with H(2)O(2). Biochem Biophys Res Commun 2000; 274 (1): 57-60.
Heikkila RE, Cabbat FS, Cohen G. In vivo inhibition of superoxide dismutase in mice by diethyldithiocarbamate. J Biol Chem 1976; 251 (7): 2182-5.
Radojičić R, Borković S, Pavlović S, Nikolić A, Blagojević D, Saičić S, Spasić M. The effect of diethyldithiocarba-mate on antioxidant enzyme activities in the blood of rats. Acta Vet 2002; 52: 329-36.
Radojičić R, Spasić M, Milić B, Saičić ZS, Petrović VM. Age-related differences in the effect of diethyldithio-carbamate and cyclohexamide on the liver copper, zinc-containing superoxide dismutase in the rat. Jugoslav Physiol Pharmacol Acta 1987; 23: 227-33.
Oreščanin-Dusić Z, Milovanović S, Blagojević D, Nikolić-Kokić A, Radojičić R, Spasojević I, Spasić M. Diethyldithio-carbamate potentiates the effects of protamine sulphate in the isolated rat uterus. Redox Rep 2009; 14 (2): 48-54.
Iciek M, Włodek L. Biosynthesis and biological properties of compounds containing highly reactive, reduced sulfane sulfur. Pol J Pharmacol 2001; 53 (3): 215-59.
Davis CA, Hearn AS, Fletcher B, Bickford J, Garcia JE, Leveque V, et al. Potent anti-tumor effects of an active site mutant of human manganese-superoxide dismutase. Evolutionary conservation of product inhibition. J Biol Chem 2004; 279 (13): 12769-76.
Peled-Kamar M, Lotem J, Wirguin I, Weiner L, Hermalin A, Groner Y. Oxidative stress mediated impairment of muscle function in transgenic mice with elevated level of wild-type Cu/Zn superoxide dismutase Proc Natl Acad Sci USA 1997; 15: 94 (8): 3883-7.
Pigeolet E, Corbisier P, Houbion A, Lambert D, Michiels C, Raes M, Zachary MD, Remacle J. Glutathione peroxidase, superoxide dismutase, and catalase inactivation by peroxides and oxygen derived free radicals. Mech Ageing Dev 1990; 51 (3): 283-97.
Simović M, Spasić MB, Michelson AM. Free radicals in human myocardial reperfusion injury. Life Chem Rep 1995; 12: 227-70.
Grieve DJ, Shah AM. Oxidative stress in heart failure. More than just damage. Eur Heart J 2003; 24 (24): 2161.
Brunelli L, Yermilov V, Beckman JS. Modulation of cata-lase peroxidatic and catalatic activity by nitric oxide. Free Radic Biol Med 2001; 30 (7): 709-14.
Tsao PS, Aoki N, Lefer DJ, Johnson G 3rd, Lefer AM. Time course of endothelial dysfunction and myocardial injury during myocardial ischemia and reperfusion in the cat. Circulation 1990; 82 (4): 1402-12.
Turrens JF, Beconi M, Barilla J, Chavez UB, McCord JM. Mitochondrial generation of oxygen radicals during reo-xygenation of ischemic tissues. Free Radic Res Commun 1991; 12-13 Pt 2: 681-9.
Kastratović DA, Vasiljević ZM, Spasić BM, Peruničić PJ, Matić M, Blagojević PD, et al. Carvedilol Increases Copper-Zinc Superoxide Dismutase Activity in Patients with Acute Myocardial Infarction. Basic & Clinical Pharmacology & Toxicology 2007; 101: 138-42.
Nikolić A, Blagojević D, Stević Z, Niketić V, Saičić ZS, Spasić MB. Activities of AD enzymes in the blood of ALS patients-base for use of antioxidants in the treatment of ALS. Proceeding of the 11 Biennal Meeting of the Society for Free Radical Research International 2002 by Monduzzi Editore S.p.A.-MEDIMOND Inc. 323-6.
Barber SC, Mead RJ, Shaw PJ. Oxidative stress in ALS: a mechanism of neurodegeneration and a therapeutic target. Biochim Biophys Acta 2006; 1762 (11-12): 1051-67.
Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993; 362 (6415): 59-62.
Sathasivam S, Ince PG, Shaw PJ. Apoptosis in amyotrophic lateral sclerosis: a review of the evidence. Neuro-pathol Appl Neurobiol 2001; 27 (4): 257-74.
Tohgi H, Abe T, Yamazaki K, Murata T, Ishizaki E, Isobe C. Increase in oxidised NO products and reduction in oxidised glutathione in cerebrospinal fluid from patients with sporadic form of amyotrophic lateral sclerosis. Neurosci Lett 1999; 260 (3): 204-6.
Nikolić-Kokić A, Stević Z, Stojanović S, Blagojević PD, Jones DR, Pavlović S, Niketić V, Apostolski S, Spasić MB. Biotransformation of nitric oxide in the cerebrospinal fluid of amyotrophic lateral sclerosis patients. Redox Report 2005; 10 (5): 265-70.
Nikolić AL, Stević ZS, Blagojević D, Saičić ZS, Spasić MB. Activities of antioxidant defence enzymes in the blood of individuals with Leu144Phe mutation. Jugoslov Med Biohem 2005; 24 (2): 111-4.
Przedborski S, Donaldson DM, Murphy PL, Hirsch O, Lange D, Naini AB, et al. Blood superoxide dismutase, catalase and glutathione peroxidase activities in familial and sporadic amyotrophic lateral sclerosis. Neurodegeneration 1996; 5: 57-64.
Apostolski S, Marinković Z, Nikolić A, Blagojević D, Spasić MB, Michelson AM. Glutathione Peroxidase in Amyotrophic Lateral Sclerosis - the Effects of Selenium Supplementation. J Environ Pathol Toxicol Oncol 1998; 17 (2): 325-9.
Hinkle ED, Wiersma W, Jurs GS. Applied statistics for behavioral sciences, 3rd ed. Boston, MA: Houghton Mifflin Company, 1994.
Manley BFJ. Multivariate statistical methods. A primer. London: Chapman and Hall, 1986.
Du Bois TM, Deng C, Huang XF. Membrane phospho-lipid composition, alterations in neurotransmitter systems and schizophrenia. Progress in Neuro Psychopharma-cology Biological Psychiatry 2005; 29: 878-88.
Michelson, AM. Medical aspects of superoxide dismutase. Life Chemistry Reports 1987; 6: 1-142.
Ranjekar PK, Hinge A, Hegde MV, Ghate M, Kale A, Sita-sawad S, Wagh UV, Debsikdar VB, Mahadik SP. Decreased antioxidant enzymes and membrane essential polyunsa-turated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Res 2003; 121 (2): 109-22.
Mukherjee S, Mahadik SP, Scheffer R, Correnti EE, Kelkar H. Impared antioxidant defence at the onset of psychosis. Schizophrenia Research 1996; 19: 19-26.
Miljević C, Nikolić-Kokić A, Saičić ZS, Milosavljević M, Blagojević D, Lečić-Toševski D, et al. Correlation analysis confirms differences in antioxidant defence in the blood of type I and II schizophrenic male patients treated with anti-psychotic medication. Psychiatry Research 2010; 178: 68-72.
Crow TJ. Positive and negative schizophrenic symptoms and the role of dopamine. Br J Psychiatry 1980; 137: 383-6.
Žunić Z, Blagojević D, Spasić M, Đuić J, Nikolić A, Marković S, Saičić ZS. Low dose radiation effects on the activity of antioxidative defence in the blood of healthy examinees Health effects of low dose radiation. Challenges of the 21st century, BNES, London 1997, 214-1.