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Singlet oxygen: a potential culprit in myocardial injury?

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Abstract

The purpose of this study was to explore the role of singlet oxygen in cardiovascular injury. To accomplish this objective, we investigated the effect of singlet oxygen [generated from photoactivation of rose-bengal] on the calcium transport and Ca2+-ATPase activity of cardiac sarcoplasmic reticulum and compared these results with those obtained by superoxide radical, hydrogen peroxide and hydroxyl radical. Isolated cardiac SR exposed to rose bengal (10 nM) irradiated at (560 nm) produced a significant inhibition of Ca 2+ uptake; from 2.27 ± 0.05 to 0.62 ± 0.05 µmol Ca+/mg.min (mean ± SE) (P < 0.01) and Ca2+-ATPase activity from 2.08 ± 0.05 µmol Pi/min. mg to 0.28 ± 0.04 µmol Pi/min. mg (mean ± SE) (P < 0.01). The inhibition of calcium uptake and Ca2+-ATPase activity by rose bengal derived activatedoxygen (singlet oxygen) was dependent on the duration of exposure and intensity of light. The singlet oxygen scavengers ascorbic acid and histidine significantly protected SR Ca2+-ATPase against rose bengal derived activated oxygen species but superoxide dismutase and catalase did not attenuate the inhibition. SDS-polyacrylamide gel electrophoresis of SR exposed to photoactivated rose bengal up to 14 min, demonstrated complete loss of Ca2+-ATPase monomer band which was significantly protected by histidine. Irradiation of rose bengal also caused an 18% loss of total sulfhydryl groups of SR. On the other hand, superoxide (generated from xanthine oxidase action on xanthine) and hydroxyl radical (0.5 mM H2O2 + Fe2+ -EDTA) as well as H2O2 (12 mM) were without any effect on the 97,000 dalton Ca2+-ATPase band ofsarcoplasmic reticulum. The results suggest that oxidative damage of cardiac sarcoplasmic reticulum may be mediated by singlet oxygen. This may represent an important mechanism by which the oxidative injury to the myocardium induces both a loss of tension development and arrhythmogenesis.

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References

  1. Braunwald E, Kloner RA: Myocardial reperfusion: a double-edged sword. J Clin Inv 76: 1713–1719, 1985

    Google Scholar 

  2. Singal P, Kapur N, Dhillon K, Beamish R, Dhalla N: Role of free radicals in catecholamine-induced cardiomyopathy. Can J Physiol Pharmacol 60: 1390–1397, 1982

    Google Scholar 

  3. Kontos HA, Wei EP, Ellis EF, Jenkins LW, Povlishock JT, Rowe GT, Hess ML: Appearance of superoxide anion radical in cerebral extracellular space during increased prostaglandin synthesis in cats. Circ Res 57: 142–151, 1985

    Google Scholar 

  4. Kukreja RC, Kontos HA, Hess ML, Ellis EF: PGH synthase and lipoxygenase generate superoxide in the presence of NADH or NADPH. Circ Res 59: 612–619, 1986

    Google Scholar 

  5. Shlafer M, Myers C, Adkins S: Mitochondrial hydrogen peroxide generation and activities of glutathione peroxidase and superoxide dismutase following global ischemia. J Mol Cell Cardiol 19: 1195–1190, 1987

    Google Scholar 

  6. 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 myocardiac ischemia. J Mol Cell Cardiol 17: 145–152, 1985

    Google Scholar 

  7. Eddy LJ, Stewart JR, Jones HP, Engerson TD, McCord JM, Downey JM: Free radical-producing enzyme, xanthine oxidase, is undetectable in human hearts. Am J Physiol 22: H709-H711, 1987

    Google Scholar 

  8. Romson JL, Hook BJ, Kunkel SL, Abrams GD, Schork MA, Lucchesi BR: Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog. Circulation 67: 1016–1023, 1983

    Google Scholar 

  9. Cadenas E: Biological chemiluminescence. In: A Quintanilha (Ed.) Reactive Oxygen Species in Chemistry, Biology, and Medicine. Plenum Press, New York, 1988, pp 117–141

    Google Scholar 

  10. Kukreja RC, Weaver AB, Hess ML: Stimulated human neutrophils damage cardiac sarcoplasmic reticulum function by generation of oxidants. Biochem Biophys A 990: 198–205, 1989

    Google Scholar 

  11. Kukreja RC, Weaver AB, Hess ML: Sarcolemmal Na+, K−-ATPase: Inactivation by free radicals and neutrophil-derived oxidants. Am J Physiol 259: H1330-H1336, 1990

    Google Scholar 

  12. Hearse DJ, Kusama Y, Bernier M: Rapid electrophysiological changes leading to arrhythmias in the aerobic rat heart: photosensitization studies with rose bengal-derived reactive oxygen intermediates. Circ Res 65: 146–153, 1989

    Google Scholar 

  13. Vandeplassche G, Bernier M, Thonè F, Borgers M, Kusama Y, Hearse DJ: Singlet oxygen and myocardial injury: ultrastructural, cytochemical and electrocardiographic consequences of photoactivation of rose bengal. J Mol Cell Cardiol 22: 287–301, 1990

    Google Scholar 

  14. Meerson FZ, Kagan VE, Kozlov YP, Belkina LM: The role of lipid peroxidation in the pathogenesis of ischemic damage and the antioxidant protection of the heart. Basic Res Cardiol 77: 465–485, 1982

    Google Scholar 

  15. Pooler JP, Valenzeno DP: Dye-sensitized photodynamic inactivation of cells. Med Phys 8: 614–628, 1981

    Google Scholar 

  16. Gaudin E, Lion Y, Vorst VD: Quantum yield of singlet oxygen production by xanthene derivatives. Photochem Photobiol 37: 271–278, 1983

    Google Scholar 

  17. Kukreja RC, Okabe E, Schrier GM, Hess ML: Oxygen radicalmediated lipid peroxidation and inhibition of Ca2+-ATPase activity of cardiac sarcoplasmic reticulum. Arch Biochem Biophys 261: 447–457, 1988

    Google Scholar 

  18. Ellman GL: Tissue sulfhydryl groups. Arch Biochem Biophys 82: 70–77, 1959

    Google Scholar 

  19. Laenuuli U: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature [Lond] 227: 680–685, 1970

    Google Scholar 

  20. Freeman BA, Crapo JD: Biology of diseases. Free radicals and tissue injury. Lab Invest 47: 412–426, 1982

    Google Scholar 

  21. Anderson BL, Berry RW, Telser A: A sodium dodecyl sulfate polyacryamide gel electrophoresis system that separates peptides and proteins in the molecular weight range of 2500 to 90000. Anal Biochem 132: 365–375, 1983

    Google Scholar 

  22. Okabe E, Hess ML, Oyama M, Ito H: Characterization of free radical-mediated damage of canine cardiac sarcoplasmic reticulum. Arch Biochem Biophys 225: 164–177, 1983

    Google Scholar 

  23. Britigan BE, Pon S, Rosen GM, Lilleg DM, Buettner GR: Hydroxyl radical is not a product of the reaction of xanthine oxidase and xanthine. J Biol Chem 265: 17533–17538, 1990

    Google Scholar 

  24. Albrich JM, McCarthy CA, Hurst JK: Biological reactivity of hypochlorous acid: implications for microbicidal mechanisms of leukocyte myeloperoxidase. Proc Natl Acad Sci USA 78: 210–214, 1981

    Google Scholar 

  25. Halliwell B: Free radicals and metal ions in health and disease. Proceedings of Nutrition Society 46: 13–26, 1987

    Google Scholar 

  26. Steinbeck MJ, Kan AU, Karnovsky MJ: A chemical trap method that specifically measures intracellular singlet oxygen generation by neutrophils. The Faseb J 5: A599, 1991 (Abstr)

    Google Scholar 

  27. Nakano M, Noguchi T, Kaneda T: Mechanism of the generation of singlet oxygen in NADPH-dependent microsomal lipid peroxidation. In: O Hayaishi and K Asada (eds) Biochemical and Medical Aspects of Active Oxygen. University of Tokyo Press, Tokyo, 1977, pp 29–42

    Google Scholar 

  28. Russel GA: Deuterium isotope effects in the autoxidation of aralkyl hydrocarbons. Mechanism of the interaction of peroxy radicals. J Am Chem Soc 79: 3871–3875, 1957

    Google Scholar 

  29. Howard JA, Ingold KU: Rate constants for the self-reaction of nand sec-butyl peroxy radicals and cyclohexylperoxy radicals. The deuterium isotope effect in the termination of secondary peroxy radicals. J Am Chem Soc 90: 1056–1061, 1968

    Google Scholar 

  30. Duran N: Singlet oxygen in biological processes. In: W Adam and G Cilento (eds) Chemical and Biological Generation of Excited States. Academic Press, New York, 1982, p 345

    Google Scholar 

  31. Krinsky NI: Biological roles of singlet oxygen. In: HH Wasserman and WA Murray (eds) Singlet Oxygen. Academic Press, New York, 1979, pp 597

    Google Scholar 

  32. McCord JM: Oxygen-derived radicals: a link between reperfusion injury and inflammation. Fed Proc 46: 2402–2406, 1987

    Google Scholar 

  33. McCord JM: Oxygen-derived free radicals in post-ischemic tissue injury. N Eng J Med 313: 159–163, 1985

    Google Scholar 

  34. McCord JM, Roy RS, Schaffer SW: Free radicals and myocardial ischemia. The role of xanthine oxidase. Adv Myocardiol 5: 183–189, 1985

    Google Scholar 

  35. Arroyo CM, Kramer JH, Leiboff RH, Mergener GW, Dickens BF, Weglicki WB: Spin trapping of oxygen and carbon-centered free radicals in ischemic canine myocardium. Free Radical Biology & Medicine 3: 313–316, 1987

    Google Scholar 

  36. Loesser KE, Kearns AA, Kukreja RC, Hess ML: Ultrastructural evidence for the protective effect of histidine, a singlet oxygen scavenger in ischemia/reperfusion injury. Faseb J 1991 (Abstr)

  37. Kukreja RC, Kearns AA, Hess ML: Ischemia/reperfusion injury in the isolated rat heart: protective effects of histidine-a singlet oxygen scavenger. Faseb J 1991 (Abstr) (In press)

  38. Kim M-S, Akera T: O2 free radicals: cause of ischemia-reperfusion injury to cardiac Na+-K+-ATPase. Na+-K+-ATPase. Am J Physiol 252: H252-H257, 1987

    Google Scholar 

  39. Vinnikova AK, Kukreja RC, Kearns AA, Hess ML: Singlet oxygen-induced inhibition of isolated cardiac sarcolemmal Na+,K+ ATPase. J Mol Cell Cardiol 1992 (Abstr) (In press)

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  1. Cardiology Division, Department of Medicine, Medical College of Virginia, Box 282, 23298, Richmond, Va, USA

    Rakesh C. Kukreja, Robert L. Jesse & Michael L. Hess

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  1. Rakesh C. Kukreja
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  2. Robert L. Jesse
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  3. Michael L. Hess
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Kukreja, R.C., Jesse, R.L. & Hess, M.L. Singlet oxygen: a potential culprit in myocardial injury?. Mol Cell Biochem 111, 17–24 (1992). https://doi.org/10.1007/BF00229569

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