Grace M . Arteaga

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Mutations in striated muscle alpha-tropomyosin (alpha-TM), an essential thin filament protein, cause both dilated cardiomyopathy (DCM) and familial hypertrophic cardiomyopathy. Two distinct point mutations within alpha-tropomyosin are associated with the development of DCM in humans: Glu40Lys and Glu54Lys. To investigate the functional consequences of(More)
Current electrophoretic methods have not been optimized to fully separate post-translationally modified mutant forms of tropomyosin (Tm) from wild-type cardiac samples. We describe here a method employing a modified 2-D PAGE/2-D DIGE protocol, to fully separate native, mutant (E54K), and phosphorylated forms of Tm. Our data demonstrate the first evidence of(More)
We compared sarcomere length (SL) dependence of the Ca2+-force relation of detergent-extracted bundles of fibres dissected from the left ventricle of wild-type (WT) and transgenic mouse hearts expressing slow skeletal troponin I (ssTnI-TG). Fibre bundles from the hearts of the ssTnI-TG demonstrated a complete replacement of the cardiac troponin I (cTnI) by(More)
Tropomyosin, an essential component of the sarcomere, regulates muscle contraction through Ca(2+)-mediated activation. Familial hypertrophic cardiomyopathy (FHC) is caused by mutations in numerous cardiac sarcomeric proteins, including myosin heavy and light chains, actin, troponin T and I, myosin binding protein C, and alpha-tropomyosin. This study(More)
BACKGROUND Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease characterized by thickening of ventricular walls and decreased left ventricular chamber volume. The majority of HCM-associated mutations are found in genes encoding sarcomere proteins. Herein, we set out to functionally characterize a novel HCM-associated(More)
1. Acidosis in cardiac muscle is associated with a decrease in developed force. We hypothesized that slow skeletal troponin I (ssTnI), which is expressed in neonatal hearts, is responsible for the observed decreased response to acidic conditions. To test this hypothesis directly, we used adult transgenic (TG) mice that express ssTnI in the heart. Cardiac(More)
Ca(2+)-sensitizers are inotropic agents that modify the response of myofilaments to Ca2+, and are potentially valuable drugs in the treatment of heart failure. These agents have diverse chemical structures, and in some cases also have effects as inhibitors of phosphodiesterase activity. Advantages of their actions include vasodilation combined with(More)
Tropomyosin (TM) is involved in Ca(2+)-mediated muscle contraction and relaxation in the heart. Striated muscle alpha-TM is the major isoform expressed in the heart. The expression of striated muscle beta-TM in the murine myocardium results in a decreased rate of relaxation and increased myofilament Ca(2+) sensitivity. Replacing the carboxyl terminus (amino(More)
Although it has been suggested that in cardiac muscle the phosphorylation level of myosin regulatory light chain (RLC) correlates with frequency of stimulation, its significance in the modulation of the force-frequency and pressure-frequency relationships remains unclear. We examined the role of RLC phosphorylation on the force-frequency relation (papillary(More)
Alteration in myofilament response to Ca2+ is a major mechanism for depressed cardiac function after ischemia-reperfusion (I/R) dysfunction. We tested the hypothesis that hearts with increased myofilament response to Ca2+ are less susceptible to I/R. In one approach, we studied transgenic (TG) mice with a constitutive increase in myofilament Ca2+(More)