Showing papers on "FABP7 published in 2017"

Normal sleep requires the astrocyte brain-type fatty acid binding protein FABP7

Abstract: Sleep is found widely in the animal kingdom. Despite this, few conserved molecular pathways that govern sleep across phyla have been described. The mammalian brain-type fatty acid binding protein (Fabp7) is expressed in astrocytes, and its mRNA oscillates in tandem with the sleep-wake cycle. However, the role of FABP7 in regulating sleep remains poorly understood. We found that the missense mutation FABP7.T61M is associated with fragmented sleep in humans. This phenotype was recapitulated in mice and fruitflies bearing similar mutations: Fabp7-deficient mice and transgenic flies that express the FABP7.T61M missense mutation in astrocytes also show fragmented sleep. These results provide novel evidence for a distinct molecular pathway linking lipid-signaling cascades within astrocytes in sleep regulation among phylogenetically disparate species.

Docosahexaenoic acid up-regulates both PI3K/AKT-dependent FABP7-PPARγ interaction and MKP3 that enhance GFAP in developing rat brain astrocytes.

Abstract: The astrocyte marker, glial fibrillary acidic protein (GFAP), has essential functions in the brain, but may trigger astroglial scarring when expressed in excess Docosahexaenoic acid (DHA) is an n-3 fatty acid that is protective during brain development However, the effect of DHA on GFAP levels of developing brain remains unexplored Here, we detected that treating developing rats with DHA-enriched fish-oil caused dose-dependent GFAP augmentation We investigated the mechanism promoting GFAP, hypothesizing the participation of fatty acid-binding protein-7 (FABP7), known to bind DHA We identified that DHA stimulated FABP7 expression in astrocytes, and FABP7-silencing suppressed DHA-induced GFAP, indicating FABP7-mediated GFAP increase Further investigation proved FABP7 expression to be phosphatidylinositide 3-kinases (PI3K)/AKT and nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ)-dependent We found that PI3K/AKT activated PPARγ that triggered FABP7 expression via PPARγ-responsive elements within its gene Towards identifying FABP7-downstream pathways, we considered our previous report that demonstrated cyclin-dependent kinase-5 (CDK5)-PPARγ-protein-protein complex to suppress GFAP We found that the DHA-induced FABP7 underwent protein-protein interaction with PPARγ, which impeded CDK5-PPARγ formation Hence, it appeared that enhanced FABP7-PPARγ in lieu of CDK5-PPARγ resulted in increased GFAP PI3K/AKT not only stimulated formation of FABP7-PPARγ protein-protein complex, but also up-regulated a FABP7-independent MAP-kinase-phosphatase-3 pathway that inactivated CDK5 and hence attenuated CDK5-PPARγ Overall, our data reveal that via the proximal PI3K/AKT, DHA induces FABP7-PPARγ, through genomic and non-genomic mechanisms, and MAP-kinase-phosphatase-3 that converged at attenuated CDK5-PPARγ and therefore, enhanced GFAP Accordingly, our study demonstrates a DHA-mediated astroglial hyperactivation, pointing toward a probable injurious role of DHA in brain development

Functional analysis of fatty acid binding protein 7 and its effect on fatty acid of renal cell carcinoma cell lines

Abstract: Renal cell carcinomas (RCCs) overexpress fatty acid binding protein 7 (FABP7). We chose to study the TUHR14TKB cell line, because it expresses higher levels of FABP7 than other cell lines derived from renal carcinomas (OS-RC-2, 786-O, 769-P, Caki-1, and ACHN). FABP7 expression was detected using western blotting and real-time PCR. Cell proliferation was determined using an MTS assay and by directly by counting cells. The cell cycle was assayed using flow cytometry. Cell migration was assayed using wound-healing assays. An FABP7 expression vector was used to transfect RCC cell lines. The levels of FABP7 expressed by TUHR14TKB cells and their doubling times decreased during passage. High-passage TUHR14TKB cells comprised fewer G0/G1-phase and more S-phase cells than low-passage cells. Cell proliferation differed among subclones isolated from cultures of low-passage TUHR14TKB cells. The proliferation of TUHR14TKB cells decreased when FABP7 was overexpressed, and the cell migration property of TUHR14TKB cells were decreased when FABP7 was overexpressed. High concentrations of docosatetraenoic acid and eicosapentaenoic acid accumulated in TUHR14TKB cells that overexpressed FABP7, and docosatetraenoic acid enhanced cell proliferation. The TUHR14TKB cell line represents a heterogeneous population that does not express FABP7 when it rapidly proliferates. The differences in FABP7 function between RCC cell lines suggests that FABP7 affects cell proliferation depending on cell phenotype.