New insights into structure and function of the different types of fatty acid-binding protein
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Fatty acid binding proteins (FABPs) are small cytosolic proteins with virtually identical backbone structures that facilitate the solubility and intracellular transport of fatty acids. They may also modulate the effect of fatty acids on various metabolic enzymes and receptors and on cellular processes as signal transduction and gene expression. At least eight different types of FABP occur, each with a specific tissue distribution and possibly with a distinct function. Our studies demonstrate significant differences in ligand binding, conformational stability and surface properties between different FABP types which may point to a specific function in certain cells and tissues. For example, the preference of ileal lipid-binding protein (but not liver-type FABP) for conjugated bile acids is in accordance with a specific role in bile acid reabsorption in the ileum. Some members of the FABP family have been implicated in the regulation of cell growth and differentiation. We investigated the effect of a series of FABPs and heart-type FABP (H-FABP) mutants on cell-free protein synthesis. Human myelin-, intestinal, heart and brain-type FABP showed a dose-dependent inhibition of in vitro mRNA translation whereas adipocyte, liver and epidermal types had no effect. The inhibition was not influenced by delipidation and was not related to affinity for fatty acids. Our results indicate that some FABPs may modulate cell growth and/or differentiation by inhibition of protein synthesis by a mechanism that remains to be elucidated. Another putative function of FABPs is to protect vital cellular functions by binding and promoting metabolism of FA, thereby reducing their intracellular concentration. We investigated the putative cytoprotective role of FABP in a MDCK cell model for renal damage. No significant differences in the effects of chemical anoxia or extracellular oleate were observed between non-transfected, mock-transfected and FABP cDNA-transfected cells. Unesterified FA accumulation was not reduced in any of the FABP cDNA-transfected cell lines. Taken together, our results do not provide evidence for a cytoprotective role of FABP in this kidney cell model. In spite of the large amount of data on the three-dimensional structure, FA-binding characteristics and tissue occurrence of FABPs, the physiological role of these proteins has not been completely resolved. Extended studies on knockout mice and transgenic cell lines transfected with FABP-encoding cDNAs, in combination with signal transduction studies will certainly help to come towards a better understanding of the physiological significance of FABPs
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