Fatty acid binding proteins (FABPS) are members of a superfamily of abundant, low Mr (12-14 kd) hydrophobic ligand binding proteins widely distributed in mammalian tissues. These proteins are believed to be responsible for the intracellular transport of fatty acids, and because they comprise up to 5% of heart cytosolic protein, they have been implicated in, protecting cell and organellar membranes from the detergent-like effects of long chain fatty acids and their metabolites which accumulate in ischemia. FABPs are expressed in an interesting tissue specific manner. Heart FABP (M-FABP) is expressed in heart, liver FABP (L-FABP) is expressed in liver and intestine, intestine FABP (I-FABP) is expressed only in intestine and kidney FABP (K-FABP),is expressed only in kidney. Nothing is known about the tissue specific factors which regulate expression of the genes for FABP. Recently, isoforms of a 40 kd plasma membrane fatty acid binding protein have been isolated from heart, liver, intestine and adipose tissue. These proteins are thought to mediate saturable binding and uptake of fatty acids into cells. The molecular basis for the differences between these 40 kd plasma membrane FABPs is not known, although we have recently determined a portion of the primary structure of the heart plasma membrane FABP, providing the first structural information available on any of these proteins.
The specific aims of this project are to: (1) investigate the molecular basis tissue specific expression of the gene for M-FABP by identifying elements in the 5' flanking region of this gene which bind nuclear proteins, (2) isolate the nuclear protein factors which regulate M-FABP gene expression in heart, and (3) characterize the 40 kd plasma membrane FABPs from heart and liver, compare these proteins in peptide mapping and sequencing studies, clone and sequence the heart 40 kd plasma membrane FABP cDNA and investigate the functional properties of this protein in a model membrane system.
| Troxler, R F; Offner, G D; Jiang, J W et al. (1993) Localization of the gene for human heart fatty acid binding protein to chromosome 1p32-1p33. Hum Genet 92:563-6 |
| Offner, G D; Brecher, P; Sawlivich, W B et al. (1988) Characterization and amino acid sequence of a fatty acid-binding protein from human heart. Biochem J 252:191-8 |
