Disease relevance of FABP7

• Suppression subtractive hybridization performed on Down syndrome (DS) fetal brains revealed a differentially expressed gene, FABP7, mapped to 6q22-23 [1].
• Overexpression of MRG in human breast cancer cells significantly suppressed cell proliferation in vitro and tumor growth in an orthotopic nude mouse model [2].
• MRG was found to be expressed in normal and benign human breast tissues but not in breast carcinomas [2].
• We show that B-FABP mRNA is expressed in human malignant glioma tumor biopsies and in a subset of malignant glioma cell lines, as well as in human fetal retina and brain [3].
• Human brain-type fatty acid-binding protein (B-FABP) has been recombinantly expressed in Escherichia coli both unlabelled and 15N-enriched for structure investigation in solution using high-resolution NMR spectroscopy [4].

Psychiatry related information on FABP7

• METHODS: B-FABP and H-FABP were measured immunochemically in autopsy samples of the brain (n = 6) and in serum samples from (a) patients with mild traumatic brain injury (MTBI; n = 130) and (b) depressed patients undergoing bilateral electroconvulsive therapy (ECT; n = 14) [5].

High impact information on FABP7

• Acute mitral regurgitation (MR) was produced in 12 dogs by closed chest partial valvulectomy and the relative contributions of MR pressure gradient (MRG), the time for regurgitant flow (VSI), and the MR orifice area (MRA) to mitral regurgitant volume (MRV) assessed [6].
• Angiotensin and volume infusion induced a substantial increase in MRF which was largely dependent on an increase in MRA but not MRG, while augmentation of contractility decreased MRF accompanied by a decrease in MRA, relatively independent of MRG [6].
• By down-regulating the FABP7 expression with FABP7-specific small interfering RNAs, in vitro cell proliferation and Matrigel invasion were suppressed in two of six melanoma cell lines [7].
• These results showed that FABP7 is frequently expressed in melanoma, may be involved in cell proliferation and invasion, and may be a potential target for development of diagnostic and therapeutic methods [7].
• Induction of mammary differentiation by mammary-derived growth inhibitor-related gene that interacts with an omega-3 fatty acid on growth inhibition of breast cancer cells [8].

Biological context of FABP7

• Overexpression of FABP7 in Down syndrome fetal brains is associated with PKNOX1 gene-dosage imbalance [1].
• To elucidate the molecular basis of FABP7 overexpression and establish the relationship with chromosome 21 trisomy, the FABP7 promoter was cloned by genomic inverse PCR [1].
• The predicted amino acid sequence of this tumor-suppressing factor has a significant sequence homology to mouse mammary-derived growth inhibitor and thus was named mammary-derived growth inhibitor-related gene (MRG) [2].
• We have cloned the human B-FABP gene and have mapped it to chromosome 6q22-23 [3].
• The murine brain fatty acid binding protein (B-FABP) is encoded by a developmentally regulated gene that is expressed in radial glial cells and immature astrocytes [3].

Anatomical context of FABP7

• MRG was barely detectable in breast carcinomas, showed partial and weak expression in benign hyperplasia, but was expressed at a high level in normal breast epithelial cells [2].
• The expression of B-FABP in glial cells and its high affinity for docosahexaenoic acid, which is known to be an important component of neuronal membranes, points toward a role for B-FABP in supplying brain abundant fatty acids to the developing neuron [9].
• Id4 was co-expressed with FABP7 in microgemistocytes in ODG and in neoplastic astrocytes in OAC [10].
• Although BLBP expression in the developing central nervous system is complex, a close correlation between its expression and radial glial differentiation has been observed [11].
• Semi-thin sections revealed that astrocytic B-FABP immunoreactivity was often, but not always, associated with GP cytoplasmic granules [12].

Associations of FABP7 with chemical compounds

• The three-dimensional structure of recombinant human B-FABP in complex with oleic acid shows that the oleic acid hydrocarbon tail assumes a "U-shaped" conformation, whereas in the complex with docosahexaenoic acid the hydrocarbon tail adopts a helical conformation [9].
• The binding affinities of BLBP for oleic acid (Kd approximately 0.44 microM) and arachidonic acid (Kd approximately 0.25 microM) are similar to those reported for other FABPs, but BLBP does not bind to palmitic acid or arachidinic acid [11].
• A probable in vivo ligand for BLBP is docosahexaenoic acid (DHA), since its binding affinity (Kd approximately 10 nM) is the highest yet reported for an FABP/ligand interaction, exceeding even the affinity of retinoic acid for its binding proteins [11].
• Telencephalic cultures obtained at E12 from ethanol-treated rats displayed a reduction in the proportion of actively dividing RG progenitors, as demonstrated by 5-bromo-2'-deoxyuridine incorporation, and in the percentage of brain lipid binding protein-positive RG [13].
• MBF and PTF were determined by oxygen-15 labelled water PET, and MRG (absolute and relative) was determined by fluorine-18 fluorodeoxyglucose (FDG) PET during hyperinsulinaemic euglycaemic clamp [14].

Regulatory relationships of FABP7

• The subset of malignant glioma cell lines that express GFAP mRNA also express B-FABP mRNA [3].

Other interactions of FABP7

• Correlation of B-FABP and GFAP expression in malignant glioma [3].
• Moreover, the NMR data indicate a close structural relationship between human B-FABP and heart-type FABP with respect to fatty acid binding inside the protein cavity [4].
• Structure, mRNA expression and linkage mapping of the brain-type fatty acid-binding protein gene (FABP7) from zebrafish (Danio rerio) [15].
• In adult brain, B-FABP was significantly increased in occipital cortex of DS, and H-FABP was significantly decreased in DS (frontal, occipital and parietal cortices) and AD (frontal, temporal, occipital and parietal cortices) [16].
• In fetal brain, B-FABP and epidermal E-FABP levels were comparable in controls and DS [16].

Analytical, diagnostic and therapeutic context of FABP7

• FABP7 overexpression in DS brains was verified by real-time PCR (1.63-fold) [1].
• In situ hybridization analysis demonstrated a stage-specific MRG expression as follows [2].
• By comparing the expression profile of a melanoma cell line with those of various normal tissues using GeneChip and by confirming the actual expression of the selected genes by reverse transcription-PCR and Northern and Western blot analyses, fatty acid-binding protein 7 (FABP7), which is frequently expressed in melanomas, was identified [7].
• Furthermore, antibodies to BLBP can block glial cell differentiation in mixed primary cell cultures [11].
• To see if GP astrocytic mitochondrial pathology is also associated with an elevation in lipid binding proteins, rat brain sections were stained for brain fatty acid binding protein (B-FABP), using immunocytochemistry [12].

References