description): The central hypothesis of this proposal is that sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA) is a critical determinant of myocardial contractility. The proposal has four specific questions (aims).
Specific aim 1 : Are there homeostatic mechanisms within the cardiac myocyte that are capable of sensing perturbations in the level of SERCA and developing compensatory mechanisms? Specific aim 2: What are the functional consequences of increased or decreased SR calcium uptake on the overall calcium homeostasis within the cardiac myocyte? Specific aim 3: What are the functional consequences of altered SR calcium transport on myocardial performance.
Specific aim 4 : What is the role of SERCA in cardiac hypertrophy and heart failure? These questions will be studied in transgenic mice with an overexpression of SERCA (both SERCA2a and SERCA1a) and in transgenic mice with a decrease in SERCA (SERCA knockout mice (+/-)).

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL064140-02
Application #
6343665
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Program Officer
Reinlib, Leslie
Project Start
2000-01-15
Project End
2001-04-30
Budget Start
2001-01-01
Budget End
2001-04-30
Support Year
2
Fiscal Year
2001
Total Cost
$144,898
Indirect Cost
Name
University of Cincinnati
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Xie, Lin; Talukder, M A Hassan; Sun, Jian et al. (2015) Liposomal tetrahydrobiopterin preserves eNOS coupling in the post-ischemic heart conferring in vivo cardioprotection. J Mol Cell Cardiol 86:14-22
Kumar, Amit; Chakravarty, Harapriya; Bal, Naresh C et al. (2013) Identification of calcium binding sites on calsequestrin 1 and their implications for polymerization. Mol Biosyst 9:1949-57
Kalyanasundaram, Anuradha; Viatchenko-Karpinski, Serge; Belevych, Andriy E et al. (2012) Functional consequences of stably expressing a mutant calsequestrin (CASQ2D307H) in the CASQ2 null background. Am J Physiol Heart Circ Physiol 302:H253-61
Talukder, M A Hassan; Yang, Fuchun; Nishijima, Yoshinori et al. (2011) Detrimental effects of thyroid hormone analog DITPA in the mouse heart: increased mortality with in vivo acute myocardial ischemia-reperfusion. Am J Physiol Heart Circ Physiol 300:H702-11
Zweier, Jay L; Talukder, M A Hassan (2011) Targeting dimethylarginine dimethylaminohydrolases in pulmonary arterial hypertension: a new approach to improve vascular dysfunction? Circulation 123:1156-8
Sulaiman, M; Matta, M J; Sunderesan, N R et al. (2010) Resveratrol, an activator of SIRT1, upregulates sarcoplasmic calcium ATPase and improves cardiac function in diabetic cardiomyopathy. Am J Physiol Heart Circ Physiol 298:H833-43
Talukder, M A Hassan; Zweier, Jay L; Periasamy, Muthu (2009) Targeting calcium transport in ischaemic heart disease. Cardiovasc Res 84:345-52
Talukder, M A Hassan; Yang, Fuchun; Nishijima, Yoshinori et al. (2009) Reduced SERCA2a converts sub-lethal myocardial injury to infarction and affects postischemic functional recovery. J Mol Cell Cardiol 46:285-7
Gupta, Subash C; Varian, Kenneth D; Bal, Naresh C et al. (2009) Pulmonary artery banding alters the expression of Ca2+ transport proteins in the right atrium in rabbits. Am J Physiol Heart Circ Physiol 296:H1933-9
Bhupathy, Poornima; Babu, Gopal J; Ito, Makoto et al. (2009) Threonine-5 at the N-terminus can modulate sarcolipin function in cardiac myocytes. J Mol Cell Cardiol 47:723-9

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