Summary
In an attempt to clarify the mechanism of sarcoplasmic reticulum (SR) dysfunction during the genesis of irreversible damage in the ischemic-reperfused myocardium, the changes in SR Ca2+-pumping ATPase (Ca2+-activated, Mg2+-dependent ATPase; Ca2+-ATPase) activity were studied during ischemia and subsequent reperfusion in the isolated perfused guinea pig heart preparation and correlated with the accumulation of calcium in the myocardium. Although the SR Ca2+-ATPase activity was not affected by ischemia of 40 min, reperfusion of the ischemic myocardium resulted in a definite time-dependent decrease in the enzyme activity. The reduction of SR Ca2+-ATPase activity was associated with a concomitant decrease in the enzyme concentration in the isolated SR and was in a good correlation with a substantial accumulation within the mhocardium. As the results indicated the possibility that proteolytic degradation by a calcium-activated protease(s) was responsible for the reduction of enzyme activity, we examined for the possible involvement of calcium-activated neutral protease (CANP). However, SR Ca2+-ATPase obtained either from the normal hearts or from the hearts after 40-min ischemia was found to be quite resistant to proteolytic actions of the two forms of CANP, i.e., μCANP and mCANP partially purified from the guinea pig heart. These results suggest that a destructive process leading to the degradation of SR Ca2+-ATPase is activated by reperfusion, but not by ischemia per se, and that CANP is not implicated in the degradation of SR Ca2+-ATPase.
Similar content being viewed by others
References
Akiyama K, Konno N, Yanagishita T, Tanno F, Katagiri T (1986) Ultrastructural changes in the sarcoplasmic reticulum in acute myocardial ischemia. Jpn Circ J 50:829–838
Amory A, Foury F, Goffeau A (1980) The purified plasma membrane ATPase of the yeast Shizosaccharomyces pombe forms a phosphorylated intermediate. J Biol Chem 255:9353–9357
Blom J, Verdouw PD, Lamers JMT (1987) Sarcoplasmic reticulum function in the ischemic myocardium. Biomed Biochim Acta 46:S589-S592
Caroni P, Carafoli F (1981) The Ca2+-pumping ATPase of heart sarcolemma. J Biol Chem 256:3263–3270
Coolican SA, Hathaway DR (1984) Effect of L-α-phosphatidylinositol on a vascular smooth muscle Ca2+-dependent protease. J Biol Chem 259:11627–11630
Croall DE, DcMartino GD (1983) Purification and characterization of calcium-dependent protease from rat heart. J Biol Chem 258:5660–5665
Goll DE, Shannon JD, Edmunds T, Sathe SK, Kleese WC, Naganis PA (1983) Properties and regulation of the Ca2+-dependent proteinase. In: De Bernard B (ed) Calcium-binding proteins. Elsevier, Amsterdam, pp 19–35
Harafuji H, Ogawa Y (1980) Re-examination of the apparent binding constant of ethyleneglycol bis (β-aminoethylether)-N,N,N′,N′-tetraacetic acid with calcium around neutral pH. J Biochem 87:1305–1312
Hess ML, Okabe E, Ash P, Kontos HA (1984) Free radical mediation of the effects of acidosis on calcium transport by cardiac sarcoplasmic reticulum in whole heart homogenates. Cardiovasc Res 18:149–157
Imai K, Wang T, Millard RW, Ashraf M, Kranias FG, Asano G, DeGende AOG, Nagao T, Solaro RJ, Schwartz A (1983) Ischemia-induced changes in canine cardiac sarcoplasmic reticulum. Cardiovasc Res. 17:696–709
Jones LR, Besch Jr HR (1984) Isolation of canine cardiac sarcolemmal vesicles. Methods Pharmacol 5:1–12
Kitazawa T (1976) Physiological significance of Ca uptake by mitochondria in the heart in comparison with that by cardiac sarcoplasmic reticulum. J Biochem 80:1129–1147
Konno N, Yanagishita T, Geshi E, Katagiri T (1987) Degradation of the cardiac sarcoplasmic reticulum in acute myocardial ischemia. Jpn Circ J 51:411–420
Krause S, Hess ML (1984) Characterization of cardiac sarcoplasmic reticulum dysfunction during short-term, normothermic, global ischemia. Circ Res 55:176–184
Kukreja R, Okabe E, Schrier G, Hess ML (1988) Oxygen radical-mediated lipid peroxidation and inhibition of Ca2+-ATPase activity of cardiac sarcoplasmic reticulum. Arch Biochem Biophys 261:447–457
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
Mellgren RL (1980) Canine cardiac calcium-dependent proteases: Resolution of two forms with different requirement for calcium. FEBS Lett 109:129–133
Neely JR, Liebermeister H, Battersby EJ, Morgan HE (1967) Effects of pressure development on oxygen consumption by isolated rat heart. Am J Physiol 212:804–814
O'Farrell PH (1975) High resolution two dimensional electrophoresis of proteins. J Biol Chem 250:4007–4021
Ohtsuka Y, Tanaka H (1983) Purification of new calcium activated protease (low calcium requiring form) and comparison to high calcium requiring form. Biochem Biophys Res Commun 111:700–709
Okabe E, Hess ML, Oyama M, Ito H (1983) Characterization of free radical-mediated damage of canine sarcoplasmic reticulum. Arch Biochem Biophys 225:164–177
Rapundalo ST, Briggs FN, Feher JJ (1986) Effects of ischemia on the isolation and function of canine cardiac sarcoplasmic reticulum. J Mol Cell Cardiol 18:837–851
Reimer KA, Jennings RB (1986) Myocardial ischemia, hypoxia and infarction. In: Fozzard HA, Haber A, Jennings RB, Morgan HE (eds) The heart and cardiovascular system. Raven Press, New York, pp 1133–1201
Shiga T, Nakazawa M, Imai S (1987) Ventricular pressure-heart rate product before induction of ischemia as a determinant of the reperfusion-induced accumulation of calcium within myocardium. Jpn J Pharmacol 45:379–387
Suzuki K, Kawashima S, Imahori K (1985) Structure and function of Ca2+-activated protease. In: Ebashi S, Endo M, Imahori K, Kakiuchi S, Nishizuka Y (eds) Calcium regulation in biological systems. Academic Press, New York, pp 213–226
Toba K, Katagiri T, Takeyama Y (1978) Studies on the cardiac sarcoplasmic reticulum in myocardial infarction. Jpn Circ J 42:447–453
Wang T, Nakamura J, Schwartz A (1984) Cardiac sarcoplasmic reticulum. Purification of Ca2+ ATPase. Methods Pharmacol 5:39–47
Wuytack F, Racymaekers L, De Shutter G, Casteels R (1982) Demonstration of the phosphointermediates of the Ca2+-transport ATPase in a microsomal fraction and in a (Ca2++Mg2+)-ATPase purified from smooth muscle by means of calmodulin affinity chromatography. Biochim Biophys Acta 693:45–52
Author information
Authors and Affiliations
Additional information
This study was supported in part by a Grant-in-Aid to Y. Y. from the Ministry of Education, Science and Culture of Japan.
Rights and permissions
About this article
Cite this article
Yoshida, Y., Shiga, T. & Imai, S. Degradation of sarcoplasmic reticulum calcium-pumping ATPase in ischemic-reperfused myocardium: Role of calcium-activated neutral protease. Basic Res Cardiol 85, 495–507 (1990). https://doi.org/10.1007/BF01931495
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01931495