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(Circulation. 1995;92:3220-3228.)
© 1995 American Heart Association, Inc.
Articles |
Unchanged Protein Levels of SERCA II and Phospholamban but Reduced Ca2+ Uptake and Ca2+-ATPase Activity of Cardiac Sarcoplasmic Reticulum From Dilated Cardiomyopathy Patients Compared With Patients With Nonfailing Hearts
From the Universität zu Köln, Medizinische Klinik III, Joseph-Stelzmannstr 9, D-50924 Köln, and the Max Delbrück Zentrum für Molekulare Medizin, Robert-Rössle Str 10, D-13125 Berlin-Buch (P.K., E.-G.K.), Germany.
Background The aim of the present study was to investigate whether Ca2+ uptake into the sarcoplasmic reticulum (SR) is altered in failing human myocardium resulting from dilated cardiomyopathy.
Methods and Results Ca2+-ATPase (SERCA II) activity and Ca2+-dependent 45Ca2+ uptake (oxalate supported, steady state) in isolated vesicles from the SR (VSR) and in crude membrane preparations (CSR) (free Ca2+, 0.01 to 100 µmol/L) from nonfailing (donor hearts, n=13) and terminally failing (heart transplants, dilated cardiomyopathy, n=17) human myocardium were studied. In the same hearts, protein levels (Western blot analysis) and mRNA levels (Northern blot analysis) of SERCA II and phospholamban were measured. Increasing concentrations of Ca2+ were followed by an increased Ca2+-ATPase activity and Ca2+ uptake. Ca2+ uptake activity and Ca2+-ATPase activity in CSR preparations from failing myocardium were significantly reduced compared with nonfailing hearts (Ca2+-ATPase, 163±8 and 125±7 nmol ATP/mg protein per minute for nonfailing tissue and failing tissue in New York Heart Association [NYHA] class IV, respectively; Ca2+ uptake, 7.1±0.8 and 3.5±0.3 nmol/mg protein per minute in CSR from nonfailing and NYHA class IV hearts, respectively; P<.05). In contrast, no significant difference was measured in VSR. In the same preparations (CSR and VSR), both SERCA II and phospholamban levels (Western blot technique with monoclonal antibodies) were unchanged in failing compared with nonfailing tissue. mRNA expression relative to GAPDH mRNA for SERCA IIa and for phospholamban was significantly reduced in failing human myocardium (P<.05).
Conclusions These findings provide evidence that in failing human myocardium caused by dilated cardiomyopathy, protein levels of SERCA II and phospholamban are unchanged even though mRNA levels for SERCA II and phospholamban and the SERCA II function are reduced compared with nonfailing myocardium.
Key Words: calcium • contractility • heart failure • sarcoplasmic reticulum
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B. J.J.M. Brundel, I. C. Van Gelder, R. H. Henning, A. E. Tuinenburg, L. E. Deelman, R. G. Tieleman, J. G. Grandjean, W. H. Van Gilst, and H. J.G.M. Crijns Gene expression of proteins influencing the calcium homeostasis in patients with persistent and paroxysmal atrial fibrillation Cardiovasc Res, May 1, 1999; 42(2): 443 - 454. [Abstract] [Full Text] [PDF]
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U. Kirchhefer, W. Schmitz, H. Scholz, and J. Neumann Activity of cAMP-dependent protein kinase and Ca2+/calmodulin-dependent protein kinase in failing and nonfailing human hearts Cardiovasc Res, April 1, 1999; 42(1): 254 - 261. [Abstract] [Full Text] [PDF]
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B. O'Rourke, D. A. Kass, G. F. Tomaselli, S. Kaab, R. Tunin, and E. Marban Mechanisms of Altered Excitation-Contraction Coupling in Canine Tachycardia-Induced Heart Failure, I : Experimental Studies Circ. Res., March 19, 1999; 84(5): 562 - 570. [Abstract] [Full Text] [PDF]
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K. Dipla, J. A. Mattiello, K. B. Margulies, V. Jeevanandam, and S. R. Houser The Sarcoplasmic Reticulum and the Na+/Ca2+ Exchanger Both Contribute to the Ca2+ Transient of Failing Human Ventricular Myocytes Circ. Res., March 5, 1999; 84(4): 435 - 444. [Abstract] [Full Text] [PDF]
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G. Hasenfuss, W. Schillinger, S. E. Lehnart, M. Preuss, B. Pieske, L. S. Maier, J. Prestle, K. Minami, and H. Just Relationship Between Na+-Ca2+–Exchanger Protein Levels and Diastolic Function of Failing Human Myocardium Circulation, February 9, 1999; 99(5): 641 - 648. [Abstract] [Full Text] [PDF]
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S. Currie and G. L. Smith Enhanced phosphorylation of phospholamban and downregulation of sarco/endoplasmic reticulum Ca2+ ATPase type 2 (SERCA 2) in cardiac sarcoplasmic reticulum from rabbits with heart failure Cardiovasc Res, January 1, 1999; 41(1): 135 - 146. [Abstract] [Full Text] [PDF]
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M. Anger, A.-M. Lompre, O. Vallot, F. Marotte, L. Rappaport, and J.-L. S. MD Cellular Distribution of Ca2+ Pumps and Ca2+ Release Channels in Rat Cardiac Hypertrophy Induced by Aortic Stenosis Circulation, December 1, 1998; 98(22): 2477 - 2486. [Abstract] [Full Text] [PDF]
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Y. Sato, D. G. Ferguson, H. Sako, G. W. Dorn II, V. J. Kadambi, A. Yatani, B. D. Hoit, R. A. Walsh, and E. G. Kranias Cardiac-specific Overexpression of Mouse Cardiac Calsequestrin Is Associated with Depressed Cardiovascular Function and Hypertrophy in Transgenic Mice J. Biol. Chem., October 23, 1998; 273(43): 28470 - 28477. [Abstract] [Full Text] [PDF]
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H. K. B. SIMMERMAN and L. R. JONES Phospholamban: Protein Structure, Mechanism of Action, and Role in Cardiac Function Physiol Rev, October 1, 1998; 78(4): 921 - 947. [Abstract] [Full Text] [PDF]
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F. Schroder, R. Handrock, D. J. Beuckelmann, S. Hirt, R. Hullin, L. Priebe, R. H. G. Schwinger, J. Weil, and S. Herzig Increased Availability and Open Probability of Single L-Type Calcium Channels From Failing Compared With Nonfailing Human Ventricle Circulation, September 8, 1998; 98(10): 969 - 976. [Abstract] [Full Text] [PDF]
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P. A Doevendans, M. J. Daemen, E. D de Muinck, and J. F Smits Cardiovascular phenotyping in mice Cardiovasc Res, July 1, 1998; 39(1): 34 - 49. [Abstract] [Full Text] [PDF]
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O. Zolk, M. Flesch, G. Nickenig, P. Schnabel, and M. Bohm Alteration of intracellular Ca2+-handling and receptor regulation in hypertensive cardiac hypertrophy: insights from Ren2-transgenic rats Cardiovasc Res, July 1, 1998; 39(1): 242 - 256. [Abstract] [Full Text] [PDF]
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L. Priebe and D. J. Beuckelmann Simulation Study of Cellular Electric Properties in Heart Failure Circ. Res., June 15, 1998; 82(11): 1206 - 1223. [Abstract] [Full Text] [PDF]
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G. Hasenfuss Alterations of calcium-regulatory proteins in heart failure Cardiovasc Res, February 1, 1998; 37(2): 279 - 289. [Full Text] [PDF]
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R. M Phillips, P. Narayan, A. M Gomez, K. Dilly, L. R Jones, W.J. Lederer, and R. A Altschuld Sarcoplasmic reticulum in heart failure: central player or bystander? Cardiovasc Res, February 1, 1998; 37(2): 346 - 351. [Full Text] [PDF]
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M. A Movsesian and R. H.G Schwinger Calcium sequestration by the sarcoplasmic reticulum in heart failure Cardiovasc Res, February 1, 1998; 37(2): 352 - 359. [Full Text] [PDF]
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M. Meyer and W. H Dillmann Sarcoplasmic reticulum Ca2+-ATPase overexpression by adenovirus mediated gene transfer and in transgenic mice Cardiovasc Res, February 1, 1998; 37(2): 360 - 366. [Abstract] [Full Text] [PDF]
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P. P de Tombe Altered contractile function in heart failure Cardiovasc Res, February 1, 1998; 37(2): 367 - 380. [Abstract] [Full Text] [PDF]
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R. Handrock, F. Schroder, S. Hirt, A. Haverich, C. Mittmann, and S. Herzig Single-channel properties of L-type calcium channels from failing human ventricle Cardiovasc Res, February 1, 1998; 37(2): 445 - 455. [Abstract] [Full Text] [PDF]
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K. R Sipido, T. Stankovicova, W. Flameng, J. Vanhaecke, and F. Verdonck Frequency dependence of Ca2+ release from the sarcoplasmic reticulum in human ventricular myocytes from end-stage heart failure Cardiovasc Res, February 1, 1998; 37(2): 478 - 488. [Abstract] [Full Text] [PDF]
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A. R.W. Money-Kyrle, C. H. Davies, H. K. Ranu, P. O'Gara, N. Singh Kent, P. A. Poole-Wilson, and S. E. Harding The role of cAMP in the frequency-dependent changes in contraction of guinea-pig cardiomyocytes Cardiovasc Res, February 1, 1998; 37(2): 532 - 540. [Abstract] [Full Text] [PDF]
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C. F. McTiernan, B. H. Lemster, C. Frye, S. Brooks, A. Combes, and A. M. Feldman Interleukin-1ß Inhibits Phospholamban Gene Expression in Cultured Cardiomyocytes Circ. Res., October 19, 1997; 81(4): 493 - 503. [Abstract] [Full Text]
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R. H. G. Schwinger, K. Brixius, U. Bavendiek, S. Hoischen, J. Müller-Ehmsen, B. Bölck, and E. Erdmann Effect of Cyclopiazonic Acid on the Force-Frequency Relationship in Human Nonfailing Myocardium J. Pharmacol. Exp. Ther., October 1, 1997; 283(1): 286 - 292. [Abstract] [Full Text]
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R. J. Hajjar, U. Schmidt, J. X. Kang, T. Matsui, and A. Rosenzweig Adenoviral Gene Transfer of Phospholamban in Isolated Rat Cardiomyocytes : Rescue Effects by Concomitant Gene Transfer of Sarcoplasmic Reticulum Ca2+-ATPase Circ. Res., August 19, 1997; 81(2): 145 - 153. [Abstract] [Full Text]
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K. Brixius, M. Pietsch, S. Hoischen, J. Muller-Ehmsen, and R. H. G. Schwinger Effect of inotropic interventions on contraction and Ca2+ transients in the human heart J Appl Physiol, August 1, 1997; 83(2): 652 - 660. [Abstract] [Full Text] [PDF]
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K. L. Koss and E. G. Kranias Phospholamban: A Prominent Regulator of Myocardial Contractility Circ. Res., December 1, 1996; 79(6): 1059 - 1063. [Full Text]
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M. Flesch, R. H.G. Schwinger, F. Schiffer, K. Frank, M. Sudkamp, F. Kuhn-Regnier, G. Arnold, and M. Bohm Evidence for Functional Relevance of an Enhanced Expression of the Na+-Ca2+ Exchanger in Failing Human Myocardium Circulation, September 1, 1996; 94(5): 992 - 1002. [Abstract] [Full Text]
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Z. Wang, B. Nolan, W. Kutschke, and J. A. Hill Na+-Ca2+ Exchanger Remodeling in Pressure Overload Cardiac Hypertrophy J. Biol. Chem., May 18, 2001; 276(21): 17706 - 17711. [Abstract] [Full Text] [PDF]
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C. Communal, M. Sumandea, P. de Tombe, J. Narula, R. J. Solaro, and R. J. Hajjar Functional consequences of caspase activation in cardiac myocytes PNAS, April 30, 2002; 99(9): 6252 - 6256. [Abstract] [Full Text] [PDF]
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