Disease relevance of Fabp1

• We report here that p14 is the liver fatty acid binding protein [1].
• The nucleotide sequence of p14 cDNA clones, isolated by screening a rat liver cDNA library in bacteriophage lambda gt11 using p14 antiserum, was completely identical to part of the sequence reported for liver fatty acid binding protein [1].
• All of the fatty acids associated with I-FABP were saturated while 30% of the E. coli fatty acids bound to L-FABP were unsaturated (16:1, 18:1, 18:2) [2].
• In search of the significance of the interaction, rat L-FABP cDNA in the sense and antisense orientations was transfected into a subline of the rat hepatoma HTC cell line that did not express L-FABP [3].
• Coexistent hepatocytic lesions, i.e., mixed basophilic adenomas, exhibited considerable morphological heterogeneity, often slightly basophilic cytoplasm, and variable immunostain of cytoplasmic p14 during interphase [4].

High impact information on Fabp1

• During tumor promotion of carcinogenesis in vivo, these groups of genotoxic and nongenotoxic carcinogens act on the normal process by which L-FABP, functioning as a specific receptor of unsaturated fatty acids or their metabolites, promotes hepatocyte proliferation [5].
• The hepatic carcinogen N-2-fluorenylacetamide (2-acetylaminofluorene) was shown previously to interact specifically with its target protein, liver fatty acid binding protein (L-FABP), early during hepatocarcinogenesis in rats [3].
• Linoleic acid at 10(-6) M increased cell number almost 3-fold (38% vs. 14%; P less than 0.0001) and thymidine incorporation nearly 5-fold (23.2% vs. 4.9%; P less than 0.001) in the L-FABP-expressing cells compared to that in the transfected nonexpressing cells [3].
• Liver fatty acid binding protein (L-FABP) is the principal target protein of the hepatic carcinogen N-(2-fluorenyl)acetamide (2-acetylaminofluorene) in rat liver [6].
• Hepatocytes in normal rat liver were found previously to contain a cytoplasmic 14,000-dalton polypeptide (p14) that is associated with mitosis and is the principal early covalent target of activated metabolites of the carcinogen N-2-fluorenylacetamide (2-acetylaminofluorene) [1].

Chemical compound and disease context of Fabp1

• The sterol binding specificity of rat recombinant liver fatty acid binding protein (L-FABP) and intestinal fatty acid binding protein (I-FABP) was characterized with [3H]cholesterol and a fluorescent sterol analog dehydroergosterol [7].
• Both the enzymes of peroxisomal fatty acid beta-oxidation and the liver fatty acid-binding protein (L-FABP) are induced in the liver by peroxisome proliferators, such as clofibrate (CF), as well as high fat diets [8].
• Also, the level of L-FABP/mRNA correlated inversely with the degree of fatty liver in ethanol-fed rats [9].
• Liver fatty acid binding protein (L-FABP) binds avidly the arachidonic acid metabolites, hydroperoxyeicosatetraenoic acids (HPETEs) and hydroxyeicosatetraenoic acids (HETEs) [10].
• In addition to fatty acids, liver fatty acid binding protein (L-FABP) also interacts with ferriheme, which it binds with an affinity approximately one order of magnitude greater than that for oleic acid [11].

Biological context of Fabp1

• Sequence analyses have detected the presence of several related amino acid sequence blocks within L-FABP which may serve similar structural roles [12].
• The L-FABP transcription unit spans 3790 nucleotides and contains four exons (115, 173, 93, and 121 base pairs) interrupted by three introns (1454, 1224, and 610 base pairs) [12].
• LFABP is able to bind long chain fatty acids with a 2:1 stoichiometry and the crystal structure has identified two fatty acid binding sites in the binding cavity [13].
• Both L-FABP content and fatty acid uptake increased significantly during liver regeneration induced by PHx in rats [14].
• The possible role of intraperoxisomal L-FABP in lipid metabolism is discussed [15].

Anatomical context of Fabp1

• Photoaffinity labeling and protection experiments carried out on purified preparations of L-FABP paralleled the labeling results obtained in the microsomes and cytosol, confirming that L-FABP is capable of specifically binding AzBHC, warfarin, and dicoumarol [16].
• Furthermore, no alteration in the relative level of SCP mRNA associated with polysomes or in polysome size occurs at the maximum and minimum points of SCP synthesis [17].
• These results demonstrate that the alpha-helical region of LFABP is responsible for its diffusional mechanism of fatty acid transfer to membranes [18].
• The complete sequence of Z-protein showed striking homology to cellular retinoid binding proteins and peripheral nerve myelin P2 protein, which indicated the presence of a new family of cellular lipid-binding proteins diverged from a common ancestor [19].
• Localization of a portion of the liver isoform of fatty-acid-binding protein (L-FABP) to peroxisomes [15].

Associations of Fabp1 with chemical compounds

• Oleic acid, an established ligand for L-FABP, can compete with the binding of the photoaffinity probe; however, it was less effective in protecting the protein than warfarin [16].
• The striking changes in amount of rat liver SCP (sterol carrier protein) during a 24-h dark-light cycle are due to alterations in the relative synthetic rate of SCP [17].
• Pre-treatment with dexamethasone statistically reduced L-FABP levels (29%) and suppressed the regenerative process (mitotic activity) [14].
• The binding of oleoyl CoA, lysophosphatidic acid, lysophosphatidylcholine, lithocholic acid and taurolithocholate 3-sulphate to LFABP has been studied using the alpha-helical mutants [13].
• Peroxisomal L-FABP was highly inducible by clofibrate [15].

Physical interactions of Fabp1

• Binding and proximity relationships of fatty acids with recombinant rat liver fatty acid-binding protein (L-FABP) and intestinal fatty acid-binding protein (I-FABP) were studied with absorption and fluorescence spectroscopy [20].
• Quartz-crystal microbalance analysis revealed that L-FABP bound to megalin, a multiligand endocytotic receptor on PTC, in a Ca2+-dependent manner [21].

Other interactions of Fabp1

• Intestinal fatty acid binding protein (IFABP) and liver FABP (LFABP), homologous proteins expressed at high levels in intestinal absorptive cells, employ markedly different mechanisms for the transfer of fatty acids (FAs) to acceptor membranes [18].
• Although Crabp2 had been identified as one of the 16 genes differentially expressed between ACI and BUF rats with cDNA-RDA, Fabp1 and Ugt2b5 were newly identified in this study [22].
• PPAR alpha agonists increased the expression and biosynthesis of liver fatty acid-binding protein (LFABP) [23].
• Electrophoretic mobility-shift assay revealed that both PPARalpha-RXRalpha and PPARdelta-RXRalpha heterodimers, specifically and in a dose-dependent manner, bound to the two PPRE-like elements of the rat CRBPII gene as well as the known PPREs in the L-FABP and acyl-CoA oxidase genes [24].
• We have reported that dietary long-chain triacylglycerols (LCT) enhance the transcription of cellular retinol-binding protein, the type II (CRBPII) gene, and the liver-type fatty acid-binding protein (L-FABP) gene in the small intestine [24].

Analytical, diagnostic and therapeutic context of Fabp1

• Three fractions (DE-I, DE-II and DE-III) of Z-protein (fatty acid binding protein) have been isolated from rat liver cytosol by DEAE-cellulose chromatography and characterized [19].
• METHODS: In the present study, we determined the time course of L-FABP mRNA expression and L-FABP levels following 70% PHx using Northern and Western blot, respectively [14].
• BACKGROUND/AIMS: Cytoplasmic liver fatty acid binding protein (L-FABP) has been suggested to be associated with cellular mitotic activity but the changes in L-FABP mRNA and protein levels during liver regeneration following partial hepatectomy (PHx) are not clear [14].
• Analytical subcellular fractionation by a method preserving the intactness of isolated peroxisomes, two-dimensional gel electrophoresis of peroxisomal matrix proteins combined with MS analysis, and immunoelectron microscopy of liver sections demonstrate the presence of L-FABP in the matrix of peroxisomes as a soluble protein [15].
• Concurrently, a large decrease in circular dichroism molar ellipticity was observed with L-FABP but not I-FABP [25].

References