This project is directed towards the general problem of intracellular movement of lipids. The focus is on understanding the regulation of fatty acid movement and metabolism in cardiac tissue, and to determine how this regulation is altered in conditions known to affect cardiac performance. The specific emphasis is on the potential role of fatty acid binding protein (FABP) in influencing fatty acid metabolism in the heart.
The specific aims are: 1) To-study the nature and specificity of the ligand binding sites on rat heart FABP. Binding assays, NMR, and chemical modification will be employed to correlate changes in binding with structural changes. 2) To determine if FABP functions in intracellular binding and transport of fatty acid, acyl CoA and acylcarnitine. In vitro systems containing organelles with enzymes utilizing those substances will be developed. 3) To determine if heart or liver FABP interacts with specific sites on model membrane systems or biological membranes. Iodinated FABP will be used to test for binding to isolated cellular membranes or synthetic vesicle preparations. 4) To determine if changes in amount or distribution of rat heart FABP are due to transcriptional or post- transcriptional control. 5) To use cultured neonatal cells or cell suspensions from adult myocytes for studies on factors regulating FABP turnover. It is hoped that by understanding how rat heart FABP functions in the normal regulation of cardiac lipid metabolism, the possibility that alterations in normal function may be a causative factor in certain disease states can be examined.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL031195-05
Application #
3342256
Study Section
Physiological Chemistry Study Section (PC)
Project Start
1984-07-01
Project End
1992-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Boston University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Borkan, S C; Wang, Y H; Lam, K T et al. (1996) Hepatic alpha 2 mu-globulin: a potential metabolic role in the rat proximal tubule. Am J Physiol 271:F527-38
LeBoeuf, R C; Xia, Y R; Oram, J F et al. (1994) Mapping of the gene for high-density lipoprotein binding protein (Hdlbp) to proximal mouse chromosome 1. Genomics 23:296-8
Mamuya, W; Chobanian, A; Brecher, P (1992) Age-related changes in fibronectin expression in spontaneously hypertensive, Wistar-Kyoto, and Wistar rat hearts. Circ Res 71:1341-50
Mamuya, W S; Brecher, P (1992) Fibronectin expression in the normal and hypertrophic rat heart. J Clin Invest 89:392-401
Takasaki, I; Chobanian, A V; Brecher, P (1991) Biosynthesis of fibronectin by rabbit aorta. J Biol Chem 266:17686-94
Saouaf, R; Takasaki, I; Eastman, E et al. (1991) Fibronectin biosynthesis in the rat aorta in vitro. Changes due to experimental hypertension. J Clin Invest 88:1182-9
Knowlton, A A; Brecher, P; Apstein, C S (1991) Rapid expression of heat shock protein in the rabbit after brief cardiac ischemia. J Clin Invest 87:139-47
Takasaki, I; Chobanian, A V; Sarzani, R et al. (1990) Effect of hypertension on fibronectin expression in the rat aorta. J Biol Chem 265:21935-9
Kohane, D S; Sarzani, R; Schwartz, J H et al. (1990) Stress-induced proteins in aortic smooth muscle cells and aorta of hypertensive rats. Am J Physiol 258:H1699-705
Takasaki, I; Cohen, R A; Chobanian, A V et al. (1990) Effect of endothelial cell denudation on fatty acid metabolism by rabbit aorta. Am J Physiol 259:H442-7

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