Disease relevance of FABP

• These results indicate that FABP can scavenge free radicals which may be present in an ischemic/reperfused heart and, thus, may play a significant physiological role in the heart during ischemia and reperfusion [1].
• Removal of endogenous long-chain fatty acid by lipidex or storage in the frozen state lead to a destabilization of the active MDGI conformation which is accompanied by a loss of its activity with regard to growth inhibition of Ehrlich Ascites cells [2].
• Transformed Escherichia coli strain BL21 (DE3)pLysS produced functional recombinant H-FABP up to 40% of the soluble proteins [3].

Psychiatry related information on FABP

• Its heart form, H-FABP, was investigated in a small group of CJD affected patients (n = 8 ) by an immunoassay approach [4].

High impact information on FABP

• A rabbit antibody to the previously reported hepatic membrane fatty acid binding protein (FABP) gave a single line of immunologic identity between the FABPs of rat jejunum and rat liver membrane [5].
• It inhibited the binding of [14C]oleate to native MVM but not heat denatured MVM, and, in immunohistochemical studies, demonstrated the presence of the FABP in the apical and lateral portions of the brush border cells of the jejunum, but not on the luminal surface of esophagus or colon [5].
• An immunohistochemical analysis with different polyclonal and peptide directed antibodies against MDGI confirmed the in situ hybridization data with respect to the tissue-specific and differentiation-dependent MDGI expression in bovine mammary gland [6].
• Increasing amounts of MDGI mRNA were detected in the epithelial cells of embryonic mammary rudiment, in the epithelium of developing lobules and in terminal parts of ducts and lobuloalveolar epithelial cells of differentiated glands [6].
• Northern blot analysis revealed abundant MDGI mRNA in the terminally differentiated mammary gland, whereas in virgin gland, liver or pancreas transcripts were not expressed [6].

Biological context of FABP

• The cDNA for a previously described growth inhibitor, designated as mammary-derived growth inhibitor (MDGI) (Grosse, R., and P. Langen. 1989. In Handbook of Experimental Pharmacology. In press) has been cloned from a plasmid library which was derived from terminally differentiated bovine mammary gland [6].
• The data revealed extensive sequence homology of mammary-derived growth inhibitor to a family of low molecular mass hydrophobic ligand-binding proteins, among them a fatty acid-binding protein from rat heart, myelin P2, a differentiation associated protein in adipocytes (p422) and the cellular retinoic acid-binding protein [7].
• A full-length cDNA for bovine heart fatty-acid-binding protein (H-FABP) was cloned from a lambda gt11 cDNA library established from bovine heart muscle [8].
• Identification of a human heart FABP pseudogene located on chromosome 13 [9].
• Human myelin, intestinal, heart and brain FABP showed a dose-dependent inhibition of in vitro mRNA translation [10].

Anatomical context of FABP

• In the course of our studies on the structural diversity of the isoforms of cardiac fatty acid-binding proteins (cFABPs), a cardiac-type FABP from the matrix of bovine heart mitochondria was purified to homogeneity and obtained as a single 15-kDa protein with an isoelectric point of 4 [11].
• There was a geographical gradient of MDGI mRNA concentration in bovine mammary gland reaching a maximum in the proximal parts of the tissue [6].
• Transport and utilization of fatty acids (FA) in cells is a multistep process that includes adsorption to and movement across the plasma membrane and binding to intracellular fatty acid binding proteins (FABP) in the cytosol [12].
• The more effective binding of the FA metabolite, 13-HODE, than its precursor 18:2 by FABP may help protect cellular membranes from potential damage by monohydroxy fatty acids and may contribute a pathway for entry of 13-HODE into the nucleus [12].
• Ribosome display was applied to select streptavidin-binding peptides in vitro from 2x10(13) molecules of the library each encoding FABP with 15 contiguous random amino acid residues at its N terminus [13].

Associations of FABP with chemical compounds

• The complex of fatty-acid-binding protein (FABP) from bovine heart (cFABP, pI4.9) with endogenous lipid was crystallized in the presence of ammonium sulfate as precipitant [14].
• H-FABP isolated from bovine heart begins with an N-acetylated valine residue, however, as derived from analysis of the tryptic, amino-terminal-blocked peptide and the molecular mass of the peptide obtained via secondary-ion mass spectrometry [8].
• The heterologous FABP was present in yeast cells in two isoforms having pI values of about 5 and was able to bind oleic acid [15].
• When FABP, ACBP and [1-14C]hexadecanoyl-CoA were mixed, hexadecanoyl-CoA could be shown to be bound to ACBP only [16].
• Compared to detection methods involving prechromatographic addition of bromosulfophthalein or radiolabeled fatty acids to cytosolic proteins, the post-chromatographic binding assay offers the advantage of leaving the bulk of the FABP preparation free of these marker ligands [17].

Physical interactions of FABP

• Myristic acid-FABP complexes serve as substrates for the Delta(9)-desaturase at mixing rates of >250 rpm [18].

Regulatory relationships of FABP

• H-FABP expression is clearly detected after that of the transcription factor myogenin which is upregulated immediately upon onset of differentiation and after that of the typical muscle enzyme creatine kinase [19].

Other interactions of FABP

• The second aspect studied was the effect of synthetic peptide analogs to the C-terminus (amino acid residues 121-131) of bovine mammary gland FABP on cell proliferation, as a result of the interaction of these peptides with the ectodomain of CD36 [20].
• Data suggest that when myristic acid is bound to FABP in the form of protein-monomer complexes, its activation to the CoA derivative is not necessary for it to be desaturated by the Delta(9)-desaturase when using mixing rates of >250 rpm [18].
• Our results suggest that FABP scavenges O2-, OH. and OCl. as indicated by the FABP inhibition of O2- -dependent reduction of cytochrome c, OH.-dependent hydroxybenzoic acid formation and OCl.-mediated chemiluminescence response [1].

Analytical, diagnostic and therapeutic context of FABP

• By use of in situ hybridization technique transcription of MDGI in the developing bovine mammary gland was analyzed [6].
• Fine mapping of the bovine heart fatty acid-binding protein gene (FABP3 ) to BTA2q45 by fluorescence in situ hybridization and radiation hybrid mapping [21].
• Quantitation of the FABP is accomplished by counting the protein-bound radioactivity in the supernatant fraction after a brief centrifugation step [17].
• We have adopted a polymerase chain reaction approach to identify and clone a cDNA that contains the complete coding sequence of a novel fatty acid binding protein (FABP) from a rat brain lambda gt10 library [22].
• Gel filtration (Sephadex G-75) of white matter cytosol of adult female rats resolved the fatty acid-binding activity in two peaks: A (Vo) and B (12-14 KDa; FABP) [23].

References