Molecular and Physiological Effects of Overexpressing Striated Muscle β-Tropomyosin in the Adult Murine Heart

作者：Mariappan Muthuchamy, Ingrid L. Grupp, Günter Grupp, Barbara A. O’Toole, Ann B. Kier, Gregory P. Boivin, Jon C. Neumann, David F. Wieczorek · 发表于：Journal of Biological Chemistry · 年份：1995 · DOI：10.1074/jbc.270.51.30593 · 被引用次数：155 · 研究领域：Cardiomyopathy and Myosin Studies、Muscle Physiology and Disorders、Cardiovascular Effects of Exercise

Tropomyosins comprise a family of actin-binding proteins that are central to the control of calcium-regulated striated muscle contraction. To understand the functional role of tropomyosin isoform differences in cardiac muscle, we generated transgenic mice that overexpress striated muscle-specific beta-tropomyosin in the adult heart. Nine transgenic lines show a 150-fold increase in beta-tropomyosin mRNA expression in the heart, along with a 34-fold increase in the associated protein. This increase in beta-tropomyosin message and protein causes a concomitant decrease in the level of alpha-tropomyosin transcripts and their associated protein. There is a preferential formation of the alpha beta-heterodimer in the transgenic mouse myofibrils, and there are no detectable alterations in the expression of other contractile protein genes, including the endogenous beta-tropomyosin isoform. When expression from the beta-tropomyosin transgene is terminated, alpha-tropomyosin expression returns to normal levels. No structural changes were observed in these transgenic hearts nor in the associated sarcomeres. Interestingly, physiological analyses of these hearts using a work-performing model reveal a significant effect on diastolic function. As such, this study demonstrates that a coordinate regulatory mechanism exists between alpha- and beta-tropomyosin gene expression in the murine heart, which results in a functional correlation between alpha- and beta-tropomyosin isoform content and ca...