Disease relevance of FABP5

• Maternal EFABP concentrations were significantly higher in mothers who delivered boys than in those who delivered girls [21.7 (2.3) vs 15.4 (1.7) microg/L, P = 0.028] and correlated with newborn birth weight (r = 0.266, P = 0.045) [1].
• We studied the differential expression of mRNAs between the primary tumour samples of SCC of the oral tongue and their metastasis by differential display analysis and identified a gene, FABP5, coding for Epidermal fatty acid binding protein (E-FABP-GenBank Accession ) [2].
• To characterize E-FABP with respect to ligand-binding properties and tertiary structure, we cloned the respective cDNA, overexpressed the protein in Escherichia coli and purified it to homogeneity by a combination of ion-exchange and size-exclusion chromatographic steps with a yield of 30 mg/L broth [3].
• The protein comigrated with PA-FABP as determined by 2D gel analysis of [35S]-methionine-labeled proteins expressed by transformed human amnion (AMA) cells transfected with clone 1592 using the vaccinia virus expression system and reacted with a rabbit polyclonal antibody raised against 2D gel purified PA-FABP [4].
• More interestingly, epidermal fatty acid-binding protein (E-FABP) and fatty acid-binding protein, adipocyte-type (A-FABP), were detected in liver cells but not in hepatoma cells [5].

Psychiatry related information on FABP5

• We recently showed that H-FABP, a protein highly homologous to E-FABP and A-FABP identified in this study, is a potential marker of Creutzfeldt-Jakob disease and stroke [6].

High impact information on FABP5

• Epidermal fatty acid-binding protein (E-FABP), previously characterized in human keratinocytes, is a cytoplasmic protein of 15 kD that specifically binds fatty acids (FAs) [7].
• By immunohistochemistry, we show that E-FABP is expressed in endothelial cells of the microvasculature of the placenta, heart, skeletal muscle, small intestine, lung, and renal medulla [7].
• Interestingly, in lung, a tissue of endodermal origin, E-FABP staining was also localized to secretory cells, ie, Clara cells, goblet cells, and probably a subpopulation of pneumocytes [7].
• RESULTS: Mean (SE) adiponectin concentrations in breast milk were 13.7 (0.8), range 3.9-30.4 microg/L; AFABP concentrations 26.7 (4.4), range 1.2-137.0 microg/L; EFABP concentrations 18.1 (1.4), range 0.8-47.0 microg/L; and leptin concentrations 0.50 (0.05), range 0-1.37 microg/L [1].
• CONCLUSIONS: Concentrations of adiponectin, AFABP, and EFABP in human breast milk are related to nutritional variables of mothers and newborns and thus may play a role in the protective effects of breastfeeding [1].

Chemical compound and disease context of FABP5

• Here we have expressed PA-FABP in Escherichia coli as a fusion protein containing an NH2-terminal hexa-His tag followed by a factor Xa cleavage site [8].
• Repetitive exposure of human skin to SDS resulted in a gradual increase in erythema scoring and TEWL associated with the upregulation of proliferative cells as measured by the expression of Ki-67-antigen and of differentiation markers, visualized by increased expression of involucrin and epidermal-fatty-acid binding protein (E-FABP) [9].
• This study shows lack of E-FABP upregulation after a single application of dithranol on uninvolved skin of patients with psoriasis [10].

Biological context of FABP5

• METHODS: We used ELISA to measure adiponectin, adipocyte and epidermal fatty acid binding proteins (AFABP, EFABP), and leptin concentrations in human breast milk obtained from 59 mothers 48 h after initiation of lactation [1].
• We resequenced 4.7 kb of the FABP5 gene in the parental population of an Iberian x Landrace cross (IBMAP), identifying seven SNPs arranged in two distinct FABP5 haplotypes [11].
• We describe the crystal structure of human epidermal-type fatty acid binding protein (E-FABP) that was recently found to be highly upregulated in human psoriatic keratinocytes [3].
• Human epidermal-type fatty acid-binding protein (E-FABP) belongs to a family of intracellular 14-15 kDa lipid-binding proteins, whose functions have been associated with fatty acid signalling, cell growth, regulation and differentiation [12].
• The upregulation of PA-FABP was confirmed by Northern blotting and conventional and whole mount labelling of human epidermis [13].

Anatomical context of FABP5

• FABP5, hsp28, and tropomyosin 9220 were also highly upregulated in quiescent keratinocytes indicating that their increased levels in the differentiated cells may be due to loss of proliferative activity [14].
• The presence of E-FABP in tissues other than skin (heart, intestine and adipose tissue) excludes its specific role in fatty acid metabolism in epithelial cells or its involvement in skin lipid-barrier function [15].
• Probable interaction between S100A7 and E-FABP in the cytosol of human keratinocytes from psoriatic scales [16].
• Epidermal-type fatty acid-binding protein (E-FABP), a protein related to the intracellular trafficking of fatty acids, is expressed in melanocytic tumours but not in normal human melanocytes [17].
• In contrast, lesional psoriatic epidermis strongly expressed E-FABP in all suprabasal layers, like nonkeratinized oral mucosa [18].

Associations of FABP5 with chemical compounds

• Squalene, cholesterol and retinoic acid isomers showed no affinity, suggesting that E-FABP displays high specificity for fatty acids [15].
• Structure-binding relation experiments revealed a high affinity of E-FABP for stearic acid which decreased on reduction of the number of carbon atoms or introduction of double bonds into the fatty acid chain [15].
• Using purified E-FABP and S100A7, the complex can be reconstituted only in presence of EDTA [19].
• E-FABP has a Mr of approximately 15 kDa and binds oleic acid with high affinity but does not bind all-trans-, 13-cis- and 9-cis-retinoic acid nor all-trans-retinol [20].
• The carbazole- and indole-based inhibitors displayed approximately 10-fold preferences over human H-FABP and E-FABP, and are highly selective against I-FABP [21].

Physical interactions of FABP5

• E-FABP interacts with S100A7 [17].
• Skin-derived antileukoproteinase (SKALP) and epidermal fatty acid-binding protein (E-FABP): two novel markers of the psoriatic phenotype that respond differentially to topical steroid [22].

Other interactions of FABP5

• We found a significant correlation between AFABP and EFABP concentrations (r = 0.593, P <0.0001) [1].
• These data indicate that formation of the E-FABP-S100A7 complex and its FA-binding function might be regulated at least by bivalent cations [19].
• All FABP types, except E-FABP, I-FABP and I-LBP interacted with 1-anilinonaphtalene-8-sulphonic acid (ANS) [23].
• The first procedure, which is illustrated with the expression of cDNAs encoding the fatty acid binding protein 5 (FABP 5), psoriasin and stratifin, makes use of the in vitro transcription/translation assay marketed by Promega [24].
• Additionally, E-FABP levels correlated with the amount of EpCAM in permanent squamous cell carcinoma lines and in vivo in primary head and neck carcinomas [25].

Analytical, diagnostic and therapeutic context of FABP5

• Microarray analysis indicates an important role for FABP5 and putative novel FABPs on a Western-type diet [26].
• Southern blotting and sequencing of the cloned RT-PCR products demonstrate that endothelial E-FABP is identical to keratinocyte E-FABP [7].
• Northern blot analysis showed that PA-FABP mRNA is indeed highly up-regulated in psoriatic keratinocytes [4].
• By using confocal microscopy we show that S100A7 and E-FABP are co-localized in the cytoplasm of differentiating keratinocytes from lesional psoriatic skin [19].
• Molecular cloning and expression of a novel keratinocyte protein (psoriasis-associated fatty acid-binding protein [PA-FABP]) that is highly up-regulated in psoriatic skin and that shares similarity to fatty acid-binding proteins [4].

References