© 1999 American Heart Association, Inc.
Original Contribution |
Identification and Expression of 
-Isoforms of the Multifunctional Ca2+/Calmodulin-Dependent Protein Kinase in Failing and Nonfailing Human Myocardium
From the Max Delbrück Center for Molecular Medicine (B.H., E.-G.K., P.K.), Berlin-Buch, and the German Heart Institute (R.M., R.H.), Berlin, Germany.
Correspondence to Dr Peter Karczewski, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str 10, 13122 Berlin-Buch, Germany. E-mail pkarcze{at}mdc-berlin.de
Abstract—Despite its
importance for the regulation of heart function, little is known about
the isoform expression of the multifunctional
Ca2+/calmodulin-dependent protein kinase
(CaMKII) in human myocardium. In this study, we
investigated the spectrum of CaMKII isoforms 
2,
3, 4, 8, and
9 in human striated muscle tissue. Isoform
3 is characteristically expressed in cardiac muscle. In
skeletal muscle, specific expression of a new isoform termed
11 is demonstrated. Complete sequencing of human
2 cDNA, representing all common features of
the investigated CaMKII subclass, revealed its high homology to the
corresponding rat cDNA. Comparative semiquantitative reverse
transcription–polymerase chain reaction analyses from left
ventricular tissues of normal hearts and from patients
suffering from dilated cardiomyopathy showed a
significant increase in transcript levels of isoform 3
relative to the expression of
glyceraldehyde-3-phosphate dehydrogenase in diseased
hearts (101.6±11.0% versus 64.9±9.9% in the nonfailing group;
P<0.05, n=6). Transcript levels of the other
investigated cardiac CaMKII isoforms remained unchanged. At the protein
level, by using a subclass-specific antibody, we observed a similar
increase of a -CaMKII–specific signal (7.2±1.0 versus 3.8±0.7
optical density units in the nonfailing group; P<0.05,
n=4 through 6). The diseased state of the failing hearts was confirmed
by a significant increase in transcript levels for atrial
natriuretic peptide (292.9±76.4% versus 40.1±3.2% in
the nonfailing group; P<0.05, n=3 through 6). Our data
characterize for the first time the -CaMKII isoform expression
pattern in human hearts and demonstrate changes in this expression
pattern in heart failure.
Key Words: Ca2+/calmodulin-dependent protein kinase II • -CaMKII • human cardiac and skeletal muscle • dilated cardiomyopathy
This article has been cited by other articles:
 |
|
 |
|
  S. Wagner, E. Hacker, E. Grandi, S. L. Weber, N. Dybkova, S. Sossalla, T. Sowa, L. Fabritz, P. Kirchhof, D. M. Bers, et al. Ca/Calmodulin Kinase II Differentially Modulates Potassium Currents Circ Arrhythmia Electrophysiol, June 1, 2009; 2(3): 285 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Backs, T. Backs, S. Neef, M. M. Kreusser, L. H. Lehmann, D. M. Patrick, C. E. Grueter, X. Qi, J. A. Richardson, J. A. Hill, et al. The {delta} isoform of CaM kinase II is required for pathological cardiac hypertrophy and remodeling after pressure overload PNAS, February 17, 2009; 106(7): 2342 - 2347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. von Lewinski, J. Kockskamper, D. Zhu, H. Post, A. Elgner, and B. Pieske Reduced Stretch-Induced Force Response in Failing Human Myocardium Caused by Impaired Na+-Contraction Coupling Circ Heart Fail, January 1, 2009; 2(1): 47 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. London Understanding Cardiac Calcium Channelopathies Circulation, November 25, 2008; 118(22): 2221 - 2222. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, S. Tandan, J. Cheng, C. Yang, L. Nguyen, J. Sugianto, J. L. Johnstone, Y. Sun, and J. A. Hill Ca2+/Calmodulin-dependent Protein Kinase II-dependent Remodeling of Ca2+ Current in Pressure Overload Heart Failure J. Biol. Chem., September 12, 2008; 283(37): 25524 - 25532. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. F. Couchonnal and M. E. Anderson The Role of Calmodulin Kinase II in Myocardial Physiology and Disease Physiology, June 1, 2008; 23(3): 151 - 159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Backs, T. Backs, S. Bezprozvannaya, T. A. McKinsey, and E. N. Olson Histone Deacetylase 5 Acquires Calcium/Calmodulin-Dependent Kinase II Responsiveness by Oligomerization with Histone Deacetylase 4 Mol. Cell. Biol., May 15, 2008; 28(10): 3437 - 3445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Pang, C. Yan, K. Natarajan, M. E. Cavet, M. P. Massett, G. Yin, and B. C. Berk GIT1 Mediates HDAC5 Activation by Angiotensin II in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., May 1, 2008; 28(5): 892 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Chen, X. Zhang, D. M. Harris, V. Piacentino III, R. M. Berretta, K. B. Margulies, and S. R. Houser Reduced effects of BAY K 8644 on L-type Ca2+ current in failing human cardiac myocytes are related to abnormal adrenergic regulation Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2257 - H2267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bossuyt, K. Helmstadter, X. Wu, H. Clements-Jewery, R. S. Haworth, M. Avkiran, J. L. Martin, S. M. Pogwizd, and D. M. Bers Ca2+/Calmodulin-Dependent Protein Kinase II{delta} and Protein Kinase D Overexpression Reinforce the Histone Deacetylase 5 Redistribution in Heart Failure Circ. Res., March 28, 2008; 102(6): 695 - 702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ikeda, M. Hoshijima, and K. R. Chien Toward Biologically Targeted Therapy of Calcium Cycling Defects in Heart Failure Physiology, February 1, 2008; 23(1): 6 - 16. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Guo, X. Ai, T. R. Shannon, S. M. Pogwizd, and D. M. Bers Intra Sarcoplasmic Reticulum Free [Ca2+] and Buffering in Arrhythmogenic Failing Rabbit Heart Circ. Res., October 12, 2007; 101(8): 802 - 810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Zhu, A. Y.-H. Woo, D. Yang, H. Cheng, M. T. Crow, and R.-P. Xiao Activation of CaMKII{delta}C Is a Common Intermediate of Diverse Death Stimuli-induced Heart Muscle Cell Apoptosis J. Biol. Chem., April 6, 2007; 282(14): 10833 - 10839. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Maier and D. M. Bers Role of Ca2+/calmodulin-dependent protein kinase (CaMK) in excitation-contraction coupling in the heart Cardiovasc Res, March 1, 2007; 73(4): 631 - 640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Anderson Multiple downstream proarrhythmic targets for calmodulin kinase II: Moving beyond an ion channel-centric focus Cardiovasc Res, March 1, 2007; 73(4): 657 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yang, W.-Z. Zhu, M.-l. Joiner, R. Zhang, C. V. Oddis, Y. Hou, J. Yang, E. E. Price, L. Gleaves, M. Eren, et al. Calmodulin kinase II inhibition protects against myocardial cell apoptosis in vivo Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H3065 - H3075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. London CaM Kinase Inhibition: Apply Directly to the Heart? Circ. Res., November 10, 2006; 99(10): 1027 - 1028. [Full Text] [PDF]
|
|
|
|
|
|
M. S.C. Khoo, J. Li, M. V. Singh, Y. Yang, P. Kannankeril, Y. Wu, C. E. Grueter, X. Guan, C. V. Oddis, R. Zhang, et al. Death, Cardiac Dysfunction, and Arrhythmias Are Increased by Calmodulin Kinase II in Calcineurin Cardiomyopathy Circulation, September 26, 2006; 114(13): 1352 - 1359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Guo, T. Zhang, R. Mestril, and D. M. Bers Ca2+/Calmodulin-Dependent Protein Kinase II Phosphorylation of Ryanodine Receptor Does Affect Calcium Sparks in Mouse Ventricular Myocytes Circ. Res., August 18, 2006; 99(4): 398 - 406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kohlhaas, T. Zhang, T. Seidler, D. Zibrova, N. Dybkova, A. Steen, S. Wagner, L. Chen, J. Heller Brown, D. M. Bers, et al. Increased Sarcoplasmic Reticulum Calcium Leak but Unaltered Contractility by Acute CaMKII Overexpression in Isolated Rabbit Cardiac Myocytes Circ. Res., February 3, 2006; 98(2): 235 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Backs and E. N. Olson Control of Cardiac Growth by Histone Acetylation/Deacetylation Circ. Res., January 6, 2006; 98(1): 15 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Ai, J. W. Curran, T. R. Shannon, D. M. Bers, and S. M. Pogwizd Ca2+/Calmodulin-Dependent Protein Kinase Modulates Cardiac Ryanodine Receptor Phosphorylation and Sarcoplasmic Reticulum Ca2+ Leak in Heart Failure Circ. Res., December 9, 2005; 97(12): 1314 - 1322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mattiazzi, C. Mundina-Weilenmann, C. Guoxiang, L. Vittone, and E. Kranias Role of phospholamban phosphorylation on Thr17 in cardiac physiological and pathological conditions Cardiovasc Res, December 1, 2005; 68(3): 366 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Woischwill, P. Karczewski, H. Bartsch, H.-P. Luther, M. Kott, H. Haase, and I. Morano Regulation of the human atrial myosin light chain 1 promoter by Ca2+-calmodulin-dependent signaling pathways FASEB J, April 1, 2005; 19(6): 503 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zayzafoon, K. Fulzele, and J. M. McDonald Calmodulin and Calmodulin-dependent Kinase II{alpha} Regulate Osteoblast Differentiation by Controlling c-fos Expression J. Biol. Chem., February 25, 2005; 280(8): 7049 - 7059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wang, W. Zhu, S. Wang, D. Yang, M. T. Crow, R.-P. Xiao, and H. Cheng Sustained {beta}1-Adrenergic Stimulation Modulates Cardiac Contractility by Ca2+/Calmodulin Kinase Signaling Pathway Circ. Res., October 15, 2004; 95(8): 798 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Zhang and J. H. Brown Role of Ca2+/calmodulin-dependent protein kinase II in cardiac hypertrophy and heart failure Cardiovasc Res, August 15, 2004; 63(3): 476 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. H.T. Wehrens, S. E. Lehnart, S. R. Reiken, and A. R. Marks Ca2+/Calmodulin-Dependent Protein Kinase II Phosphorylation Regulates the Cardiac Ryanodine Receptor Circ. Res., April 2, 2004; 94(6): e61 - e70. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Zhang, S. Miyamoto, and J. H. Brown Cardiomyocyte Calcium and Calcium/Calmodulin-dependent Protein Kinase II: Friends or Foes? Recent Prog. Horm. Res., January 1, 2004; 59(1): 141 - 168. [Abstract] [Full Text]
|
|
|
|
|
|
J. BORLAK and T. THUM Hallmarks of ion channel gene expression in end-stage heart failure FASEB J, September 1, 2003; 17(12): 1592 - 1608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ji, B. Li, T. D. Reed, J. N. Lorenz, M. A. Kaetzel, and J. R. Dedman Targeted Inhibition of Ca2+/Calmodulin-dependent Protein Kinase II in Cardiac Longitudinal Sarcoplasmic Reticulum Results in Decreased Phospholamban Phosphorylation at Threonine 17 J. Biol. Chem., June 27, 2003; 278(27): 25063 - 25071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Maier, T. Zhang, L. Chen, J. DeSantiago, J. H. Brown, and D. M. Bers Transgenic CaMKII{delta}C Overexpression Uniquely Alters Cardiac Myocyte Ca2+ Handling: Reduced SR Ca2+ Load and Activated SR Ca2+ Release Circ. Res., May 2, 2003; 92(8): 904 - 911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Zhang, L. S. Maier, N. D. Dalton, S. Miyamoto, J. Ross Jr, D. M. Bers, and J. H. Brown The {delta}C Isoform of CaMKII Is Activated in Cardiac Hypertrophy and Induces Dilated Cardiomyopathy and Heart Failure Circ. Res., May 2, 2003; 92(8): 912 - 919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mishra, H. N. Sabbah, J. C. Jain, and R. C. Gupta Reduced Ca2+-calmodulin-dependent protein kinase activity and expression in LV myocardium of dogs with heart failure Am J Physiol Heart Circ Physiol, March 1, 2003; 284(3): H876 - H883. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Colomer, L. Mao, H. A. Rockman, and A. R. Means Pressure Overload Selectively Up-Regulates Ca2+/Calmodulin-Dependent Protein Kinase II in Vivo Mol. Endocrinol., February 1, 2003; 17(2): 183 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Lorenz, M. H. Riddervold, E. A. H. Beckett, S. A. Baker, and B. A. Perrino Differential autophosphorylation of CaM kinase II from phasic and tonic smooth muscle tissues Am J Physiol Cell Physiol, November 1, 2002; 283(5): C1399 - C1413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Rosen Blunderbuss to Mickey Mouse: The Evolution of Antiarrhythmic Targets Circulation, September 3, 2002; 106(10): 1180 - 1182. [Full Text] [PDF]
|
|
|
|
|
|
Y. Wu, J. Temple, R. Zhang, I. Dzhura, W. Zhang, R. Trimble, D. M. Roden, R. Passier, E. N. Olson, R. J. Colbran, et al. Calmodulin Kinase II and Arrhythmias in a Mouse Model of Cardiac Hypertrophy Circulation, September 3, 2002; 106(10): 1288 - 1293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bartel, B. Hoch, D. Vetter, and E.-G. Krause Expression of Human Angiotensinogen-Renin in Rat: Effects on Transcription and Heart Function Hypertension, February 1, 2002; 39(2): 219 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Boknik, I. Heinroth-Hoffmann, U. Kirchhefer, J. Knapp, B. Linck, H. Luss, T. Muller, W. Schmitz, O.-E. Brodde, and J. Neumann Enhanced protein phosphorylation in hypertensive hypertrophy Cardiovasc Res, September 1, 2001; 51(4): 717 - 728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wu, R. J. Colbran, and M. E. Anderson Calmodulin kinase is a molecular switch for cardiac excitation -contraction coupling PNAS, February 27, 2001; 98(5): 2877 - 2881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Colomer and A. R. Means Chronic Elevation of Calmodulin in the Ventricles of Transgenic Mice Increases the Autonomous Activity of Calmodulin-Dependent Protein Kinase II, Which Regulates Atrial Natriuretic Factor Gene Expression Mol. Endocrinol., August 1, 2000; 14(8): 1125 - 1136. [Abstract] [Full Text]
|
|
|
|
|
|
M. E. Anderson Connections Count : Excitation-Contraction Meets Excitation-Transcription Coupling Circ. Res., April 14, 2000; 86(7): 717 - 719. [Full Text] [PDF]
|
|
|
|
|
|
T. Netticadan, R. M. Temsah, K. Kawabata, and N. S. Dhalla Sarcoplasmic Reticulum Ca2+/Calmodulin-Dependent Protein Kinase Is Altered in Heart Failure Circ. Res., March 17, 2000; 86(5): 596 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. He and M. C. LaPointe Interleukin-1{beta} Regulates the Human Brain Natriuretic Peptide Promoter via Ca2+-Dependent Protein Kinase Pathways Hypertension, January 1, 2000; 35(1): 292 - 296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Krasko, H. C. Schroder, S. Perovic, R. Steffen, M. Kruse, W. Reichert, I. M. Muller, and W. E. G. Muller Ethylene Modulates Gene Expression in Cells of the Marine Sponge Suberites domuncula and Reduces the Degree of Apoptosis J. Biol. Chem., October 29, 1999; 274(44): 31524 - 31530. [Abstract] [Full Text] [PDF]
|
|