Disease relevance of FABP3

• Polymorphisms in fatty acid-binding protein-3 (FABP3) - putative association with type 2 diabetes mellitus [1].
• Human breast cancer cells transfected with a MDGI expression construct exhibited differentiated morphology, reduced proliferation rate, reduced clonogenicity in soft agar, and reduced tumorgenicity in nude mice relative to mock-transfected or untransfected controls [2].
• MDGI immunoreactivity was detected in epithelial cells of human breast tissue, but not on ductal carcinoma cells on the same sections [2].
• Immunohistochemical distribution of heart-type fatty acid-binding protein immunoreactivity in normal human tissues and in acute myocardial infarct [3].
• We conclude that aberrant expression of FABPs, especially H-FABP may alter membrane fluidity and signal transduction, and consequently could be involved in cellular dysfunction in neurodegenerative disorders [4].

Psychiatry related information on FABP3

• Heart type fatty acid binding protein (H-FABP) is decreased in brains of patients with Down syndrome and Alzheimer's disease [4].
• It permitted the detection of H-FABP directly in plasma in the range of 10-1500 ng/mL which is the relevant range for clinical decision-making [5].
• 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) [6].
• Levels of H-FABP were significantly higher in CJD patients compared to AD and DLB in CSF [7].
• Our results suggest that H-FABP might be a useful biomarker for the differentiation between the dementias examined if levels in CSF and serum are determined in parallel [7].

High impact information on FABP3

• Selective inhibition of endogenous MDGI expression in MEC by antisense phosphorothioate oligonucleotides suppresses appearance of alveolar end buds and lowers the beta-casein level in organ cultures [8].
• We also demonstrated that homozygous deletion and point mutation are not common mechanisms for silencing of the MDGI gene in human breast neoplasms [9].
• We now report that hypermethylation of HpaII and HhaI sites upstream of the first exon of the MDGI gene, and a SacII site in the first intron, occurs frequently in human breast cancer cell lines [9].
• The gene encoding mammary-derived growth inhibitor (MDGI), a protein previously purified from bovine mammary gland and shown to have modest antiproliferative activity for human breast cancer cells in vitro, is demonstrated to function as a potent tumor suppressor gene [2].
• Our results suggest that MDGI is a strong candidate for the distal 1p breast tumor suppressor gene [2].

Chemical compound and disease context of FABP3

• In an unmatched case-control study of 63 non-immune European patients with uncomplicated (n = 52) and complicated (n = 11) falciparum malaria, serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), heart-type fatty acid-binding protein (H-FABP), myoglobin, troponin T and creatin kinase-muscle brain were compared [10].

Biological context of FABP3

• The inhibitory effect of PPARgamma-siRNA was supported by testing human PPARgamma mRNA and adipogenic associated genes using reverse transcription polymerase chain reaction (RT-PCR) to adiponectin receptor 1 and 2 as well as examination of fatty acid binding protein 3 (FABP3) expression, an adipocyte-specific marker [11].
• By means of fluorescence in situ hybridization this processed pseudogene could be assigned chromosome 13q13-q14, whereas the gene for human H-FABP (FABP3) resides on chromosome 1p32-p33 [12].
• The zebrafish FABP3 exhibited the greatest amino acid sequence identity to fish and mammalian heart-type FABPs [13].
• Dinucleotide repeat in the third intron of the FABP3/MDGI putative tumor suppressor gene [14].
• In an effort to identify polymorphic markers in potential candidate genes for type 2 diabetes, we have sequenced the full gene of FABP3, including the -1,500bp promoter region [1].

Anatomical context of FABP3

• FABP3 is the dominating FABP in skeletal muscle [15].
• In mammary epithelial cells MDGI is associated with neither mitochondria nor endoplasmic reticulum, and is expressed in a strictly developmental-dependent spatial and temporal pattern [16].
• H-FABP positivity was associated with the depth of invasion (p <0.0001), vascular invasion (p <0.0001), lymph node metastasis (p <0.0001), hepatic metastasis (p=0.0011), stage of the carcinoma (p <0.0001) and FAS status of the carcinoma (p=0.0476) [17].
• METHODS: We correlated serum levels of a cytosolic marker (heart-type fatty acid-binding protein) and a myofibril marker (troponin T) with the severity of symptoms (based on the New York Heart Association [NYHA] class), neurohumoral derangement, and subsequent cardiac events in 56 patients with chronic heart failure [18].
• The method was applied to three test cases: one complex involving muscle fatty acid-binding protein (mFABP) and two complexes involving the leukocyte function-associated antigen 1 (LFA-1) I-domain [19].

Associations of FABP3 with chemical compounds

• CONCLUSIONS: Stearate, elaidate and oleate each adopt highly similar U-shaped conformations when they bind to M-FABP within a large interior binding cavity, which also contains 13 ordered water molecules [20].
• Significant correlations were found between heart-type fatty acid-binding protein levels and plasma levels of A-type natriuretic peptide (r = 0.45, P = 0.0004), B-type natriuretic peptide (r = 0.66, P <0.0001), and norepinephrine (r = 0.36, P = 0.006) [18].
• We demonstrate that the antiestrogens 4-hydroxytamoxifen (4-OH tamoxifen) and ICI 182780 (ICI) stimulate MDGI expression in vitro [21].
• Under estrogen-free conditions, the half-life of MDGI mRNA in control explants was approximately 6 h [21].
• In summary, we showed that troglitazone markedly induces PPARgamma, ALBP, and mFABP mRNA abundance in muscle cultures from both nondiabetic and type II diabetic subjects [22].

Physical interactions of FABP3

• Comparison of the predicted secondary sequence of CD36 with that of human muscle fatty acid binding protein suggested that a potential binding site for the fatty acid on CD36 may exist in its extracellular segment between residues 127 and 279 [23].
• Expression of human liver fatty acid-binding protein in Escherichia coli and comparative analysis of its binding characteristics with muscle fatty acid-binding protein [24].

Regulatory relationships of FABP3

• Still, FABP4 is markedly less expressed than FABP3, which is the generally accepted dominating FABP in skeletal muscle tissue [15].

Other interactions of FABP3

• A comparison of the three-dimensional structure of human muscle fatty acid-binding protein and rat intestinal fatty acid-binding protein shows strong similarity [25].
• 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) [4].
• The finding that the change in UCP3 protein content correlates with the change in skeletal muscle fatty acid-binding protein content, suggests a role for UCPs in the handling of lipids as a fuel [26].
• In ECT, serum B-FABP was increased in 6% of all samples (2 of 14 patients), whereas H-FABP was above its upper reference limit (6 microg/L) in 17% of all samples (8 of 14 patients), and S100B was above its upper reference limit (0.3 microg/L) in 0.4% of all samples [6].
• A scenario is discussed in which FABPpm, FAT/CD36, and H-FABP, probably assisted by an albumin-binding protein, cooperate in the translocation of FA across the sarcolemma [27].

Analytical, diagnostic and therapeutic context of FABP3

• By logistic and multiple regression analysis, one insertion/deletion polymorphism in the 3' end (c.634+483delT) of FABP3 appeared to be weakly associated with increased risk of type 2 diabetes (OR=1.78-1.94, P=0.03-0.04) and waist/hip ratio (WHR) (P=0.03) [1].
• METHODS: Immunohistochemistry with anti-H-FABP antibody was performed in 669 gastric carcinomas and 60 tubular adenomas of the stomach [17].
• Evaluation of a strategy combining biomarker testing with echocardiography revealed that patients with a negative H-FABP test had an excellent prognosis regardless of echocardiographic findings [28].
• CONCLUSION: Serum H-FABP is a potential independent predictor of cardiac events within 6 months of patient admission and may provide prognostic information superior to cTnT in the early hours of ACS [29].
• METHODS: Serum concentrations of H-FABP and cTnT were measured on admission in 328 consecutive patients hospitalized for ACS within 6 h after the onset of chest pain [AMI, 241 (73.5%) patients; ST-segment elevation myocardial infarction, 154 (47.0%) patients; and emergent coronary angiography within 24 h after admission, 287 (87.5%) patients] [29].

References