Skip to main content
Log in

Alterations in heart sarcolemmal Ca2+-ATPase and Ca2+-binding activities due to oxygen free radicals

  • Original Contributions
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Summary

Effects of oxygen free radicals on Ca2+/Mg2+ ATPase and ATP-independent Ca2+-binding activities were examined in rat heart sarcolemma. Membranes were incubated with different oxygen radical generating media such as xanthine + xanthine oxidase, hydrogen peroxide, and hydrogen peroxide + Fe2+. In the presence of xanthine + xanthine oxidase, Ca2+ ATPase activity was stimulated and this effect was prevented by the addition of superoxide dismutase. Hydrogen peroxide also showed a significant increase in Ca2+-ATPase activity in a dose-dependent manner and this effect was blocked by catalase. On the other hand, a combination of hydrogen peroxide + Fe2+ decreased Ca2+-ATPase activity; this depression was prevented by the addition of D-mannitol. The observed change in Ca2+-ATPase activity due to oxygen free radicals was associated with changes in Vmax, whereas Ka remained unaffected. Both xanthine + xanthine oxidase and hydrogen peroxide increased whereas, hydrogen peroxide + Fe2+ inhibited the ATP-independent Ca2+-binding activities. It is suggested that oxygen free radicals may influence Ca2+ movements in the cell by altering the Ca2+/Mg2+ ATPase and Ca2+-binding activities of the membrane and these effects may be oxygen-radical species specific.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Anand MB, Chauhan MS, Dhalla NS (1977) Ca2+/Mg2+ ATPase activities of heart sarcolemma, microsome, and mitochondria. J Biochem (Tokyo) 82:1731–1739

    Google Scholar 

  2. Barrington PL, Meier CF Jr, Weglicki WB (1988) Abnormal electrical activity induced by free radical generating systems in isolated cardiocytes. J Mol Cell Cardiol 20:1163–1178

    PubMed  Google Scholar 

  3. Bers DM, Langer GA (1979) Uncoupling cation effects on cardiac contractility and sarcolemmal Ca binding. Am J Physiol 237 (Heart Circ Physiol 6):H332-H341

    PubMed  Google Scholar 

  4. Bers DM, Philipson KD, Langer GA (1981) Cardiac contractility and sarcolemmal calcium binding in several cardiac preparations. Am J Physiol 240 (Heart Cire Physiol 9):H576-H583

    PubMed  Google Scholar 

  5. Burton KP, McCord JM, Ghai G (1984) Myocardial alterations due to free-radical generation. Am J Physiol. 246:H776-H783

    PubMed  Google Scholar 

  6. Burton KP, Morris AC, Massey KD, Buja LM, Hagler HK (1988) Alterations in ionic calcium transients in cultured neonatal rat myocytes induced by exposure to free radicals can be modified by α-tocopherol. Circ 78 (Suppl II):215

    Google Scholar 

  7. Dhalla NS, Anand-Srivastava MB, Tuana BS, Khandelwal RL (1981) Solubilization of a calcium dependent adenosine triphosphatase from rat heart sarcolemma. J Mol Cell Cardiol 13:413–423

    PubMed  Google Scholar 

  8. Dhalla NS, Pierce GN, Panagia V, Singal PK, Beamish RE (1982) Calcium movements in relation to heart function. Basic Res Cardiol 77:117–139

    PubMed  Google Scholar 

  9. Dhalla NS, Singal PK (1984) Progres and problems in understanding the involvement of calcium in heart function Can J Physiol Pharmacol 62:867–873

    PubMed  Google Scholar 

  10. Dhalla NS, Smith CI, Pierce GN, Elimban V, Makino N, Khatter JC (1986) Heart sarcolemmal cation pumps and binding sites. In: Rupp H (ed) Regulation of heart function. Thiame-Stratton, New York, pp 126–136

    Google Scholar 

  11. Dhalla NS, Zhao D (1989) Cell membrane Ca2+/Mg2+ ATPase. Prog Biophys Molec Biol (in press)

  12. Freeman BA, Crapo JD (1982) Biology of Disease; free radicals and tissue injury. Lab Invest 47:412–426

    PubMed  Google Scholar 

  13. Gupta M, Singal PK (1989) Higher antioxidative capacity during a chronic stable heart hypertrophy. Circ Res 64:398–406

    PubMed  Google Scholar 

  14. Halliwell B, Grootveld M (1986) The measurement of free radical reactions in humans. FEBS Lett 213:9–14

    Google Scholar 

  15. Hammond B, Hess ML (1985) The oxygen free radical system: Potential mediator of myocardial injury. J Am Coll Cardiol 6:215–220

    PubMed  Google Scholar 

  16. Kaneko M, Beamish RE, Dhalla NS (1989) Depression of heart sarcolemmal Ca2+-pump activity by oxygen free radicals. Am J Physiol 256 (Heart Circ Physiol 25); H368-H374

    PubMed  Google Scholar 

  17. Kramer JH, Mak IT, Weglicki WB (1984) Differential sensitivity of canine cardiac sarcolemmal and microsomal enzymes to inhibition by free radical-induced lipid peroxidation. Circ Res 55:120–124

    PubMed  Google Scholar 

  18. Levedev AV, Levitsky DO, Loqinov VA, Smirov VON (1982) The effect of primary products of lipid peroxidation on the transmembrane transport of calcium ions. J Mol Cell Cardiol 14 (Suppl IV): 99–103

    Google Scholar 

  19. Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  Google Scholar 

  20. Malout NN, Meissner G (1980) Cytochemical localization of a “basic” ATPase to canine myocardial surface membrane. J Histochem Cytochem 28:1286–1294

    PubMed  Google Scholar 

  21. Matskubo MP, Singal PK, Dhalla NS (1981) Negatively charged sites and calcium binding in the isolated rat heart sarcolemma. Basic Res Cardiol 76:16–28

    PubMed  Google Scholar 

  22. MacLenman PH, Hollan PC (1975) Calcium transport in sarcoplasmic reticulum. Annu Rev Biophys Bioeng 4:377–404

    PubMed  Google Scholar 

  23. McNamara DB, Sulakhe PV, Singh JN, Dhalla NS (1974) Properties of heart sarcolemmal Na+−K+ ATPase. J Biochem 75:795–803

    PubMed  Google Scholar 

  24. Nagy IZ, Floyd RA (1984) Hydroxyl free radical reactions with amino acids and proteins studied by electron spin resonance spectroscopy and spin-traping. Biochem. Biophys Acta 790:238–250

    PubMed  Google Scholar 

  25. Panagia V, Singh JN, Anand-Srivastava MB, Pierce GN, Jasmin D, Dhalla NS (1984) Sarcolemmal alterations during the development of genetically determined cardiomyopathy. Cardiovasc Res 18:567–572

    PubMed  Google Scholar 

  26. Pierce GN, Kutryk MJB, Dhalla NS (1983) Alterations in Ca2+ binding by and composition of the cardiac sarcolemmal membrane in chronic diabetes. Proc Natl Acad Sci USA 80:5412–5416

    PubMed  Google Scholar 

  27. Pitts BJR (1979) Stoichiometry of sodium-calcium exchange in cardiac sarcolemmal vesicles. J Biol Chem 254:6232–6235

    PubMed  Google Scholar 

  28. Reeves JP, Bailey CA, Hale CC (1986) Redox modification of sodium-calcium exchange activity in cardiac sarcolemmal vesicles. J Biol Chem 261:4948–4955

    PubMed  Google Scholar 

  29. Scherer NM, Darmer DW (1986) Oxidative stress impairs the function of sarcoplasmic reticulum by oxidation of sulfydryl groups in the Ca2+-ATPase. Arch Biochem Biophys 246:589–601

    PubMed  Google Scholar 

  30. Schrier GM, Hess ML (1988) Quantitative identification of superoxide anion as a negative inotropic species. Am J Physiol 255 (Heart Circ Physiol 24):H138-H143

    PubMed  Google Scholar 

  31. Singal PK, Deally CMR, Weinberg LE (1987) Subcellular effects of adriamycin in the heart. J Mol Cell Cardiol 19:817–828

    PubMed  Google Scholar 

  32. Tomlinson CW, Lee SL, Dhalla NS (1976) Abnormalities in heart membranes and myofibrils during bacterial infective cardiomyopathy in the rabbit. Circ Res 39:82–92

    PubMed  Google Scholar 

  33. Tuana BS, Dhalla NS (1982) Purification and characterization of a Ca2+-dependent ATPase from rat heart sarcolemma. J Biol Chem 257:14440–14445

    PubMed  Google Scholar 

  34. Tuana BS, Dhalla NS (1988) Purification and characterization of a Ca2+/Mg2+ ecto-ATPase from rat heart sarcolemma. Mol Cell Biochem 81:75–88

    PubMed  Google Scholar 

  35. Tien M, Svingen BA, Aust SD (1982) An investigation into the role of hydroxyl radical in xanthine oxidase-dependent lipid peroxidation. Arch Biochem Biophys 216:142–151

    PubMed  Google Scholar 

  36. Zhao D, Dhalla NS (1988) Characterization of rat heart plasma membrane Ca2+/Mg2+ ATPase. Arch Biochem Biophys 263:281–292

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kaneko, M., Singal, P.K. & Dhalla, N.S. Alterations in heart sarcolemmal Ca2+-ATPase and Ca2+-binding activities due to oxygen free radicals. Basic Res Cardiol 85, 45–54 (1990). https://doi.org/10.1007/BF01907013

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01907013

Key words

Navigation