AJP - Heart Calcium Transients and Cell-Sarcomere
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 278: H412-H419, 2000;
0363-6135/00 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (51)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tardiff, J. C.
Right arrow Articles by Leinwand, L. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tardiff, J. C.
Right arrow Articles by Leinwand, L. A.
Vol. 278, Issue 2, H412-H419, February 2000

Expression of the beta  (slow)-isoform of MHC in the adult mouse heart causes dominant-negative functional effects

Jil C. Tardiff1, Timothy E. Hewett2, Stephen M. Factor1, Karen L. Vikstrom3, Jeffrey Robbins2, and Leslie A. Leinwand4

1 Department of Medicine, Albert Einstein College of Medicine, Bronx 10461; 3 State University of New York, Health Science Center, Syracuse 13210;2  Division of Molecular Cardiovascular Biology, Department of Pediatrics, Children's Hospital Research Foundation, Cincinnati, Ohio 45229; and 4 Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309

alpha - and beta -myosin heavy chain (MHC), the two MHC isoforms expressed in the mammalian heart, differ quantitatively in their enzymatic activities. The MHC composition of the heart can change dramatically in response to numerous stimuli, leading to the hypothesis that changes in cardiac function can be caused by myosin isoform shifts. However, this hypothesis has remained unproven because the stimuli used to generate these shifts are complex and accompanied by many additional physiological changes, including alterations in cardiac mass and geometry. Adult mouse ventricles normally express only alpha -MHC (the faster motor). To determine whether genetic alteration of the MHC isoform composition in the adult mouse heart would result in changes in cardiac chamber mass and contractility, we established transgenic mouse lines that express a Myc-tagged beta -MHC molecule (the slower motor) in adult ventricular tissue, one of which expreses 12% of its myosin as the transgene. There is no evidence of hypertrophy, induction of hypertrophic markers, and no histopathology. Myofibrillar Ca2+-activated ATPase activity is decreased by 23%, and Langendorff preparations demonstrate a significant 15% decrease in systolic function in transgenic hearts. These results suggest that even small shifts in the myosin isoform composition of the myocardium can result in physiologically significant changes in cardiac contractility and could be relevant to cardiovascular disease.

myosin heavy chain; contractility; transgenic


This article has been cited by other articles:


Home page
 Circ. Res.Home page
B. A. Colson, T. Bekyarova, M. R. Locher, D. P. Fitzsimons, T. C. Irving, and R. L. Moss
Protein Kinase A-Mediated Phosphorylation of cMyBP-C Increases Proximity of Myosin Heads to Actin in Resting Myocardium
Circ. Res., August 1, 2008; 103(3): 244 - 251.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
D. S. Hydock, C.-Y. Lien, C. M. Schneider, and R. Hayward
Effects of voluntary wheel running on cardiac function and myosin heavy chain in chemically gonadectomized rats
Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3254 - H3264.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
A. F. Martin, S. Bhatti, G. J. Pyne-Geithman, M. Farjah, V. Manaves, L. Walker, R. Franks, A. R. Strauch, and R. J. Paul
Expression and function of COOH-terminal myosin heavy chain isoforms in mouse smooth muscle
Am J Physiol Cell Physiol, July 1, 2007; 293(1): C238 - C245.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
T. J. Herron, R. Vandenboom, E. Fomicheva, L. Mundada, T. Edwards, and J. M. Metzger
Calcium-Independent Negative Inotropy by {beta}-Myosin Heavy Chain Gene Transfer in Cardiac Myocytes
Circ. Res., April 27, 2007; 100(8): 1182 - 1190.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
P. G. Laustsen, S. J. Russell, L. Cui, A. Entingh-Pearsall, M. Holzenberger, R. Liao, and C. R. Kahn
Essential Role of Insulin and Insulin-Like Growth Factor 1 Receptor Signaling in Cardiac Development and Function
Mol. Cell. Biol., March 1, 2007; 27(5): 1649 - 1664.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
J. E. Stelzer, S. L. Brickson, M. R. Locher, and R. L. Moss
Role of myosin heavy chain composition in the stretch activation response of rat myocardium
J. Physiol., February 15, 2007; 579(1): 161 - 173.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
M. L. Tschirgi, I. Rajapakse, and M. Chandra
Functional consequence of mutation in rat cardiac troponin T is affected differently by myosin heavy chain isoforms
J. Physiol., July 1, 2006; 574(1): 263 - 273.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
H. Sun, B.-G. Kerfant, D. Zhao, M. G. Trivieri, G. Y. Oudit, J. M. Penninger, and P. H. Backx
Insulin-Like Growth Factor-1 and PTEN Deletion Enhance Cardiac L-Type Ca2+ Currents via Increased PI3K{alpha}/PKB Signaling
Circ. Res., June 9, 2006; 98(11): 1390 - 1397.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
J. P. Konhilas, P. A. Watson, A. Maass, D. M. Boucek, T. Horn, B. L. Stauffer, S. W. Luckey, P. Rosenberg, and L. A. Leinwand
Exercise Can Prevent and Reverse the Severity of Hypertrophic Cardiomyopathy
Circ. Res., March 3, 2006; 98(4): 540 - 548.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
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]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
C. A. Emter, S. A. McCune, G. C. Sparagna, M. J. Radin, and R. L. Moore
Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats
Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2030 - H2038.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
T. Pelzer, V. Jazbutyte, K. Hu, S. Segerer, M. Nahrendorf, P. Nordbeck, A. W. Bonz, J. Muck, K.-H. Fritzemeier, C. Hegele-Hartung, et al.
The estrogen receptor-{alpha} agonist 16{alpha}-LE2 inhibits cardiac hypertrophy and improves hemodynamic function in estrogen-deficient spontaneously hypertensive rats
Cardiovasc Res, September 1, 2005; 67(4): 604 - 612.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
O. Dewald, S. Sharma, J. Adrogue, R. Salazar, G. D. Duerr, J. D. Crapo, M. L. Entman, and H. Taegtmeyer
Downregulation of Peroxisome Proliferator-Activated Receptor-{alpha} Gene Expression in a Mouse Model of Ischemic Cardiomyopathy Is Dependent on Reactive Oxygen Species and Prevents Lipotoxicity
Circulation, July 19, 2005; 112(3): 407 - 415.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
J. James, L. Martin, M. Krenz, C. Quatman, F. Jones, R. Klevitsky, J. Gulick, and J. Robbins
Forced Expression of {alpha}-Myosin Heavy Chain in the Rabbit Ventricle Results in Cardioprotection Under Cardiomyopathic Conditions
Circulation, May 10, 2005; 111(18): 2339 - 2346.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
V. L. M. Rundell, V. Manaves, A. F. Martin, and P. P. de Tombe
Impact of {beta}-myosin heavy chain isoform expression on cross-bridge cycling kinetics
Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H896 - H903.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C. C. Sucharov, S. M. Helmke, S. J. Langer, M. B. Perryman, M. Bristow, and L. Leinwand
The Ku Protein Complex Interacts with YY1, Is Up-Regulated in Human Heart Failure, and Represses {alpha} Myosin Heavy-Chain Gene Expression
Mol. Cell. Biol., October 1, 2004; 24(19): 8705 - 8715.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
M. C. Olsson, B. M. Palmer, B. L. Stauffer, L. A. Leinwand, and R. L. Moore
Morphological and Functional Alterations in Ventricular Myocytes From Male Transgenic Mice With Hypertrophic Cardiomyopathy
Circ. Res., February 6, 2004; 94(2): 201 - 207.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
Y. Zhong, P. J Reiser, and M. A. Matlib
Gender differences in myosin heavy chain-{beta} and phosphorylated phospholamban in diabetic rat hearts
Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2688 - H2693.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
Y. Ishibashi, M. Takahashi, Y. Isomatsu, F. Qiao, Y. Iijima, H. Shiraishi, J. M. Simsic, C. F. Baicu, J. Robbins, M. R. Zile, et al.
Role of microtubules versus myosin heavy chain isoforms in contractile dysfunction of hypertrophied murine cardiocytes
Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1270 - H1285.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Krenz, A. Sanbe, F. Bouyer-Dalloz, J. Gulick, R. Klevitsky, T. E. Hewett, H. E. Osinska, J. N. Lorenz, C. Brosseau, A. Federico, et al.
Analysis of Myosin Heavy Chain Functionality in the Heart
J. Biol. Chem., May 2, 2003; 278(19): 17466 - 17474.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
D. T. Lucas, P. Aryal, L. I. Szweda, W. J. Koch, and L. A. Leinwand
Alterations in mitochondrial function in a mouse model of hypertrophic cardiomyopathy
Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H575 - H583.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
A. G Schmidt, J. Zhai, A. N Carr, M. J Gerst, J. N Lorenz, P. Pollesello, A. Annila, B. D Hoit, and E. G Kranias
Structural and functional implications of the phospholamban hinge domain: impaired SR Ca2+ uptake as a primary cause of heart failure
Cardiovasc Res, November 1, 2002; 56(2): 248 - 259.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
T. J. Herron, F. S. Korte, and K. S. McDonald
Loaded shortening and power output in cardiac myocytes are dependent on myosin heavy chain isoform expression
Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1217 - H1222.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online