Abstract
The changes in the regulation of at mitochondrial NADP-isocitrate dehydrogenase (NADP-ICDH) in a rat heart during have been analysed. Increase of enzyme activity in the cytosol and mitochondria of the heart ischemia was detected. Catalytic properties of the mitochondrial NADP-ICDH at norm and pathology have been compared on homogeneous enzyme preparations. Enzyme from the normoxic and ischemic heart showed the same electrophoretical mobility and molecular mass. Enzyme isolated from the ischemic heart mitochondria demonstrated higher activation energy and lower thermal stability. NADP-isocitrate dehydrogenase at the normoxic and ischemic conditions exhibited different Km for substrates and regulatory behaviour in relation to ATP, ADP, 2-oxoglutarate, citrate, malate, reduced and oxidised glutathione. The inhibitory effect of the Fe2+ and H2O2 mixture associated with the generation of hydroxyl radicals was lower in the ischemic enzyme. We hypothesise that the specific features of regulation behaviour of NADP-ICDH from the ischemic tissues permits the enzyme to supply NADPH to the glutathione reductase/glutathione peroxidase system.
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Nakasava H, Arroyo C., Ichimori, K: Ischemia-reperfusion injury and toxicity of free radicals. J Mol Cell Cardiol 22(2): 13, 1990
Ruuge EK, Ledenev AN, Lakomkin VL: Free radical metabolites in myocardium during ischemia and re-perphusion. Amer J Physiol 261(4): 81–86, 1991
Guarneru G, Muskari C, Ventura C: Effect of ischemia on heart sub-mitochondrial superoxide production. Free Radicals Res Communs 1(2): 123–128, 1985
Meerson FZ: The failing heart. Adaptation and de-adaptation. N.Y.: Raven press, 1983
Skulachev VP: Role of uncoupled and non-coupled oxidations in maintenance of safely low levels of oxygen and its one-electrone reductants. Q Rev Biophys 29: 169–203, 1996
Korshunov SS, Skulachev VP, Starkov AA: High potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett 416: 15–18, 1997
Esposito LA, Melov S, Panov A, Cottrell BA, Wallace DC: Mitochondrial disease in mouse results in increased oxidative stress. Proc Natl Acad Sci USA 96(9): 4820–4825, 1999
Chambers DE, Parks DA, Patterson G, Roy R, McCord JM, Yoshida S, Parmley LF, Downey JM: Xanthine oxidase as a source of free radical damage in myocardial ischemia. J Mol Cell Cardiol 17(2): 145–152, 1985
Rao PS, Cohen MV, Mueller HS: Production of free radicals and lipid peroxides in early experimental myocardial ischemia. J Mol Cell Cardiol 15(10): 713–716, 1983
Halliwell B, Gutteridge JM: The importance of free radicals and catalytic metal ions in human diseases. Mol Aspects Med 8(2): 89–193, 1985
Skulachev VP: Membrane-linked systems, preventing superoxide formation. Bioscience Reports 17(3): 347–366, 1997
Flint DH, Tuminello JF, Emptage M: The inactivation of Fe-S cluster containing hydrolyases by superoxide. J Biol Chem 268: 22369–22376, 1993
Osipov AN, Azizova OA, Vladimirov YA: Active oxygen species and their role in the organism. Uspekhi biologicheskoi khimii 31: 180–208, 1990
Pfeifer R, Rarl G, Scholz R: Does the pentose cycle plays a major role for NADPH supply in the heart? Biol Chem Hopp-Seyler 367(10): 1061–1068, 1986
Jo SH, Son MK, Koh HJ, Lee SM, Song IH, Kim YO, Lee YS, Jeong KS, Kim WB, Park JW, Song BJ, Huh TL: Control of mitochondrial redox balance and cellular defense against oxidative damage by mitochondrial NADP-dependent isocitrate dehydrogenase. J Biol Chem 276: 16168–16176, 2001
Pastuszko A, Gromek A: Effect of free fatty acids on the activity of NADP-dependent isocitrate dehydrogenase in normal and pathological conditions. Bull Acad Pol Sci Ser Sci Biol 24(7): 415–422, 1976
Islam M, Joyce L, Bell L, Baron DN: Purification and comparative properties of isoenzymes of NADP-isocitrate dehydrogenase from rat heart and liver. Biochem J 129(5): 1003–1011, 1972
Galvez S, Gadal P: The function of the NADP-dependent isocitrate dehydrogenase isoenzymes in living organisms. Plant Science 105: 1–11, 1995
Seelig GF, Colman RF: Characterization of the physicochemical and catalytic properties of human heart NADP-dependent isocitrate dehydrogenase. Arch Biochem Biophys 188(2): 394–409, 1978
Medvedeva LV, Popova TN, Artiuykhov VG, Matasova LV, Pinheiro de Carvalho MAA: Free radical processes intensity and activity regulation of cytoplasmic NADP-isocitrate dehydrogenase in rat heart at norm and ischemia // Biochem. (Mosc) 67(6): 696–705, 2002
Lowenstein JM: The tricarboxylic acid cycle In: Metabolic Pathways. Edited by Greenberg DM. New York: Academic, p. 147–267, 1967
Luo H, Shan X, Wu J: Expression of human mitochondrial NADP-dependent isocitrate dehydrogenase during lymphocyte activation. J Cell Biochem 60: 495–507, 1996
Comte B, Vincent G, Bouchard B, Benderdour M, Des Rosiers C: Reverse flux through cardiac NADP-isocitrate dehydrogenase under normoxia and ischemia. Am J Physiol Heart Circ Physiol 283(4): H1505–H1514, 2002
Jonassen AK, Aasum E, Riemersma RA, Mjos OD, Larsen TS: Glucose-insulin-potassium reduces infarct size when administered during reperfusion. Cardiovasc Drugs Ther 14(6): 615–623, 2000
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin Phenol reagent. J Biol Chem 139: 265–275, 1951
Yu J, Steck TL: Isolation and characterization of band 3, the predominant polypeptide of the human erythrocyte membrane. J Biol Chem 250: 9170–9175, 1975
Davis BJ: Disc electrophoresis. II Method and application to serum protein Ann. N.Y. Acad Sci 121: 404–407, 1964
Maurer G: Disk Electrophoresis [Russian translation]. Mir, Moscow, 1971
Kulkarni AP, Mehrotra KN: Estimation of molecular parameters of proteins by gel chromatography on Sephadex G-150. Anal Biochem 38(1): 285–288, 1970
Kurganov BI: Allosteric enzymes. Mcy;oscow: Science, 1978
Dixon M, Webb EC: Enzymes, 3rd edn. USA Acad. Press Inc., NY, 1979
Medvedeva LV, Popova TN, Artyukhov VG, Matasova LV, Akatova RV: Oxidative status and distribution of NADP-dependent isocitrate dehydrogenase and aconitate hydratase in rat cardiomyocytes under normal conditions and during ischemia. Bull Exp Biol Med 134(2): 130–134, 2002
Meerson FZ: Pathogenesis and prevention of stress and ischemic heart injury. Moscow, Medicina, p 272, 1984
Penny JE, Kukumus JR, Tyrer JH. Eadic MJ: Quantitative oxidative enzyme histochemistry of the spinal cord. Part 2. Relation of cell size and enzyme activity to vulnerability to ischemia. J Neurol Sci 26(2): 187–192, 1975
Popova TN: Isocitrate dehydrogenases: forms, localization, properties and regulation. Biochemistry (Moscow). 58(12): 1861–1879, 1993
Smyth GE, Colman RF: Cysteinyl peptides of pig heart NADP-dependent isocitrate dehydrogenase that are modified upon inactivation by N-ethylmaleimide. J Biol Chem 266: 14918–14925, 1991
Fatania HR, Al-Nassar KE, Thomas N: Chemical modification of rat liver cytosolic NADP(+)-linked isocitrate dehydrogenase by N-ethylmaleimide. Evidence for essential sulphohydryl groups. FEBS Lett 322: 245–248, 1993
Lee SM, Huh TL, Park J-W: Inactivation of NADP(+)-dependent isocitrate dehydrogenase by reactive oxygen species. Biochimie (Paris) 83: 1057–1065, 2001
Yang ES, Richter C, Chun JS, Huh TL, Kang SS, Park JW: Inactivation of NADP(+)-dependent isocitrate dehydrogenase by nitric oxide. Free Radic Biol Med 33: 927–937, 2002
Yang JH, Yang ES, Park JW: Inactivation of NADP+-dependent isocitrate dehydrogenase by lipid peroxidation products. Free Radic Res 38(3): 241–249, 2004
Benderdour M, Charron G, DeBlois D, Comte B, Des Rosiers C: Cardiac mitochondrial NADP+-isocitrate dehydrogenase is inactivated through 4-hydroxynonenal adduct formation: an event that precedes hypertrophy development. J Biol Chem 278: 45154–45159, 2003
Kil IS, Park J-W: Regulation of mitochondrial NADP-dependent isocitrate dehydrogenase activity by glutathionylation. J Biol Chem 280(11): 10846–10854, 2005
Gatsura VV: Pharmacological correction of the energy metabolism of the ischemic myocardium. Pharmacol Ther 27(3): 297–332, 1985
Reimer KA, Hill ML, Jennings RB: Prolonged depletion of ATP and of adenine nucleotide pool due to delayed re-synthesis of adenine nucleotides following reversible myocardial injury in dogs. J Moll Cell Cardiol 13(2): 229–240, 1981
Sazanov LA, Jackson JB: Proton-translocating transhydrogenase and NAD- and NADP-linked isocitrate dehydrogenases operate in a substrate cycle which contributes to fine regulation of the tricarboxylic acid cycle activity in mitochondria. FEBS Lett 344(2–3): 109–116, 1994
Cerri C, Fici F, Scarlato G: α-Ketoglutarate induced transamination during ischemic exercise. Adv Exp Med Biol 153: 473–478, 1982
Nohl H, Jordan W: The metabolic fate of mitochondrial hydrogen peroxide. Europ J Biochem 111: 203–210, 1980
Dalle-Donne I, Giustarini D, Colombo R, Rossi R, Milzani A: Protein carbonilation in human diseases. Trends Mol Med 9: 169–176, 2003
Flagg TP, Nichols CG: Sarcolemmal KATP channels in the dark: molecular mechanisms brought to light, but physiologic consequences still in the dark. J Cardiovasc Electrophysiol 12: 1195–1198, 2001
Sundqvist KE, Heikkila J, Hassinen IE, Hiltunen JK: Role of NADP (corrected)-linked malic enzymes as regulators of the pool size of tricarboxylic acid-cycle intermediates in the perfused rat heart. Biochem J 243: 853–857, 1987
Kehrer JP, Lund LG: Cellular reducing equivalents and oxidative stress. Free Radic Biol Med 17: 65–75, 1994
Kim HJ, Kang BS, Park JW: Cellular defense against heat shock-induced oxidative damage by mitochondrial NADP+-dependent isocitrate dehydrogenase. Free RadicRes 39(4): 441–448, 2005
Kil IS, Huh TL, Lee YS, Lee YM, Park JW: Regulation of replicative senescence by NADP(+)-dependent isocitrate dehydrogenase. Free Radic Biol Med 40(1): 110–119, 2006
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Popova, T., Carvalho, M.A.A.P.d., Matasova, L. et al. Regulation of mitochondrial NADP-isocitrate dehydrogenase in rat heart during ischemia. Mol Cell Biochem 294, 97–105 (2007). https://doi.org/10.1007/s11010-006-9249-9
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DOI: https://doi.org/10.1007/s11010-006-9249-9