Brain-type Fatty Acid Binding Protein Research Articles

Stationary-to-migratory transition in glioblastoma stem-like cells driven by a fatty acid-binding protein 7-RXRα neurogenic pathway.

Glioblastoma (GBM) stem-like cells (GSCs) are crucial drivers of treatment resistance and tumor recurrence. While the concept of "migrating" cancer stem cells was proposed a decade ago, the roles and underlying mechanisms of the heterogeneous populations of GSCs remain poorly defined. Cell migration using GBM cell lines and patient-derived GSCs was examined using Transwell inserts and the scratch assay. Single-cell RNA sequencing data analysis were used to map GSC drivers to specific GBM cell populations. Xenografted mice were used to model the role of brain-type fatty acid-binding protein 7 (FABP7) in GBM infiltration and expansion. The mechanism by which FABP7 and its fatty acid ligands promote GSC migration was examined by gel shift and luciferase gene reporter assays. A subpopulation of FABP7-expressing migratory GSCs was identified, with FABP7 upregulating SOX2, a key modulator for GBM stemness and plasticity, and ZEB1, a prominent factor in GBM epithelial-mesenchymal transition and invasiveness. Our data indicate that GSC migration is driven by nuclear FABP7 through activation of RXRα, a nuclear receptor activated by polyunsaturated fatty acids (PUFAs). Infiltrative progression in GBM is driven by migratory GSCs through activation of a PUFA-FABP7-RXRα neurogenic pathway.

FABP7: a glial integrator of sleep, circadian rhythms, plasticity, and metabolic function.

Sleep and circadian rhythms are observed broadly throughout animal phyla and influence neural plasticity and cognitive function. However, the few phylogenetically conserved cellular and molecular pathways that are implicated in these processes are largely focused on neuronal cells. Research on these topics has traditionally segregated sleep homeostatic behavior from circadian rest-activity rhythms. Here we posit an alternative perspective, whereby mechanisms underlying the integration of sleep and circadian rhythms that affect behavioral state, plasticity, and cognition reside within glial cells. The brain-type fatty acid binding protein, FABP7, is part of a larger family of lipid chaperone proteins that regulate the subcellular trafficking of fatty acids for a wide range of cellular functions, including gene expression, growth, survival, inflammation, and metabolism. FABP7 is enriched in glial cells of the central nervous system and has been shown to be a clock-controlled gene implicated in sleep/wake regulation and cognitive processing. FABP7 is known to affect gene transcription, cellular outgrowth, and its subcellular localization in the fine perisynaptic astrocytic processes (PAPs) varies based on time-of-day. Future studies determining the effects of FABP7 on behavioral state- and circadian-dependent plasticity and cognitive processes, in addition to functional consequences on cellular and molecular mechanisms related to neural-glial interactions, lipid storage, and blood brain barrier integrity will be important for our knowledge of basic sleep function. Given the comorbidity of sleep disturbance with neurological disorders, these studies will also be important for our understanding of the etiology and pathophysiology of how these diseases affect or are affected by sleep.

A Dichotomous Role for FABP7 in Sleep and Alzheimer's Disease Pathogenesis: A Hypothesis.

Fatty acid binding proteins (FABPs) are a family of intracellular lipid chaperone proteins known to play critical roles in the regulation of fatty acid uptake and transport as well as gene expression. Brain-type fatty acid binding protein (FABP7) is enriched in astrocytes and has been implicated in sleep/wake regulation and neurodegenerative diseases; however, the precise mechanisms underlying the role of FABP7 in these biological processes remain unclear. FABP7 binds to both arachidonic acid (AA) and docosahexaenoic acid (DHA), resulting in discrete physiological responses. Here, we propose a dichotomous role for FABP7 in which ligand type determines the subcellular translocation of fatty acids, either promoting wakefulness aligned with Alzheimer’s pathogenesis or promoting sleep with concomitant activation of anti-inflammatory pathways and neuroprotection. We hypothesize that FABP7-mediated translocation of AA to the endoplasmic reticulum of astrocytes increases astrogliosis, impedes glutamatergic uptake, and enhances wakefulness and inflammatory pathways via COX-2 dependent generation of pro-inflammatory prostaglandins. Conversely, we propose that FABP7-mediated translocation of DHA to the nucleus stabilizes astrocyte-neuron lactate shuttle dynamics, preserves glutamatergic uptake, and promotes sleep by activating anti-inflammatory pathways through the peroxisome proliferator-activated receptor-γ transcriptional cascade. Importantly, this model generates several testable hypotheses applicable to other neurodegenerative diseases, including amyotrophic lateral sclerosis and Parkinson’s disease.

Fabp7 Is Required for Normal Sleep Suppression and Anxiety-Associated Phenotype following Single-Prolonged Stress in Mice.

Humans with post-traumatic stress disorder (PTSD) exhibit sleep disturbances that include insomnia, nightmares, and enhanced daytime sleepiness. Sleep disturbances are considered a hallmark feature of PTSD; however, little is known about the cellular and molecular mechanisms regulating trauma-induced sleep disorders. Using a rodent model of PTSD called "Single Prolonged Stress" (SPS) we examined the requirement of the brain-type fatty acid binding protein Fabp7, an astrocyte expressed lipid-signaling molecule, in mediating trauma-induced sleep disturbances. We measured baseline sleep/wake parameters and then exposed Fabp7 knock-out (KO) and wild-type (WT) C57BL/6N genetic background control animals to SPS. Sleep and wake measurements were obtained immediately following the initial trauma exposure of SPS, and again 7 days later. We found that active-phase (dark period) wakefulness was similar in KO and WT at baseline and immediately following SPS; however, it was significantly increased after 7 days. These effects were opposite in the inactive-phase (light period), where KOs exhibited increased wake in baseline and following SPS, but returned to WT levels after 7 days. To examine the effects of Fabp7 on unconditioned anxiety following trauma, we exposed KO and WT mice to the light-dark box test before and after SPS. Prior to SPS, KO and WT mice spent similar amounts of time in the lit compartment. Following SPS, KO mice spent significantly more time in the lit compartment compared to WT mice. These results demonstrate that mutations in an astrocyte-expressed gene (Fabp7) influence changes in stress-dependent sleep disturbances and associated anxiety behavior.

Crystal structure of human brain-type fatty acid-binding protein FABP7 complexed with palmitic acid.

The brain-type fatty acid-binding protein FABP7, which is expressed in astrocytes and neural progenitors, is a member of the intracellular lipid-binding protein family. This protein is not only involved in various cellular functions such as metabolism, inflammation and energy homeostasis, but also in diseases such as cognitive disorders and tumors. Structures of unsaturated fatty acids, such as oleic acid (OA) and docosahexaenoic acid (DHA), bound to FABP7 have been elucidated; however, structures of saturated fatty acids bound to FABP7 remain unknown. To better understand fatty acid recognition, here the crystal structure of human brain-type fatty acid-binding protein FABP7 complexed with palmitic acid (PA), a saturated fatty acid, is reported at a resolution of 1.6 Å. The PA bound to the fatty acid-binding pocket of FABP7 assumed a U-shaped conformation. The carboxylate moiety of PA interacted with Tyr129, Arg127 and, via a water bridge, with Arg107 and Thr54, whereas its aliphatic chain was stabilized by hydrophobic interactions with Met21, Leu24, Thr30, Thr37, Pro39, Phe58 and Asp77. Structural comparison showed that PA, OA and DHA exhibited unique binding conformations in the fatty acid-binding pocket, stabilized by distinct amino-acid interactions. The binding of PA to FABP7 exhibits a unique binding conformation when compared with other human FABPs (FABP3-FABP5 and FABP8) expressed in other tissues. Based on the crystal and fatty acid structures, it was suggested that PA, which prefers a linear form in nature, required a greater conformational change in its aliphatic chain to bind to the fatty acid-binding pocket in a U-shaped conformation, compared with the cis configurations of OA or DHA. This, together with the length of the aliphatic chain, was considered to be one of the factors determining the binding affinity of PA to FABP7. These results provide a better understanding of fatty acid recognition by FABP7 and expand the knowledge of the binding of PA to FABPs.

Relations of heart-type and brain-type fatty acid-binding proteins with postoperative cognitive dysfunction in elderly patients undergoing spinal surgery.

The aim of this study is to analyze the relations of heart-type fatty acid-binding protein (H-FABP) and brain-type fatty acid-binding protein (B-FABP) with postoperative cognitive dysfunction (POCD) in elderly patients undergoing spinal surgery. One hundred and twenty-five patients who underwent spinal surgery were enrolled in this study. According to whether patients had POCD within 5 days after surgery, the participants were divided into POCD group and non-POCD group. Before surgery and 6 h after surgery, the serum H-FABP and B-FABP contents were detected. There were 33 (26.4%) patients in POCD group, and 92 (73.60%) patients in non-POCD group. After surgery, the serum H-FABP and B-FABP contents in POCD group were significantly higher than those before surgery, respectively (p<0.05), and those in non-POCD group were significantly lower than those before surgery, respectively (p<0.05). After surgery, the serum H-FABP and B-FABP contents in POCD group were significantly higher than those in non-POCD group, respectively (p<0.05). The serum H-FABP and B-FABP contents are positively related to the occurrence of POCD in elderly patients undergoing spinal surgery.

The influence of gaseous microemboli on various biomarkers after minimized cardiopulmonary bypass.

Gaseous microemboli that originate from the cardiopulmonary bypass circuit may contribute to adverse outcome after cardiac surgery. We prospectively evaluated the influence of gaseous microemboli on the release of various biomarkers after use of a minimally invasive extracorporeal technology system. In 70 patients undergoing coronary artery bypass grafting with minimized cardiopulmonary bypass, gaseous microemboli were measured intraoperatively with a bubble counter. Intra- and postoperative biomarker levels for inflammatory response (interleukin-6, C5b-9), endothelial damage (von Willebrand factor, soluble vascular cell adhesion molecule-1), oxidative stress (malondialdehyde, 8-isoprostane, neuroketal), and neurological injury (neuron-specific enolase, brain-type fatty acid-binding protein) were analyzed using immune assay techniques. The relationship between gaseous microemboli number or volume and the incremental area under the curve (iAUC24h) or peak change for the biomarkers was calculated. All biomarkers except for malondialdehyde increased at least temporarily after coronary artery bypass grafting with a minimally invasive extracorporeal technology system. The median total gaseous microemboli number was 6,174 (interquartile range: 3,507-10,531) and the median total gaseous microemboli volume was 4.31 µL (interquartile range: 2.71-8.50). There were no significant correlations between total gaseous microemboli number or volume and iAUC24h or peak change for any of the biomarkers. After controlling for the variance of possible other predictor variables, multiple linear regression analysis showed no association between gaseous microemboli parameters and release of biomarkers. This study showed no evidence that gaseous microemboli contribute to increased biomarker levels after coronary artery bypass grafting with cardiopulmonary bypass. A reason for the absence of damage by gaseous microemboli may be the relative and considerably small amount of gaseous microemboli entering the patients in this study.

The ligand-mediated affinity of brain-type fatty acid-binding protein for membranes determines the directionality of lipophilic cargo transport

The intracellular transport of lipophilic cargoes is a highly dynamic process. In eukaryotic cells, the uptake and release of long-chain fatty acids (LCFAs) are executed by fatty-acid binding proteins. However, how these carriers control the directionality of cargo trafficking remains unclear. Here, we revealed that the unliganded archetypal Drosophila brain-type fatty acid-binding protein (dFABP) possesses a stronger binding affinity than its liganded counterpart for empty nanodiscs (ND). Titrating unliganded dFABP and nanodiscs with LCFAs rescued the broadening of FABP cross-peak intensities in HSQC spectra from a weakened protein–membrane interaction. Two out of the 3 strongest LCFA contacting residues in dFABP identified by NMR HSQC chemical shift perturbation (CSP) are also part of the 30 ND-contacting residues (out of the total 130 residues in dFABP), revealed by attenuated TROSY signal in the presence of lipid ND to apo-like dFABP. Our crystallographic temperature factor data suggest enhanced αII helix dynamics upon LCFA binding, compensating for the entropic loss in the βC-D/βE-F loops. The aliphatic tail of bound LCFA impedes the charge-charge interaction between dFABP and the head groups of the membrane, and dFABP is prone to dissociate from the membrane upon ligand binding. We therefore conclude that lipophilic ligands participate directly in the control of the functionally required membrane association and dissociation of FABPs.

Effects of FABP7 on functional recovery after spinal cord injury in adult mice.

Elucidating the mechanisms of neuronal injury is crucial for the development of spinal cord injury (SCI) treatments. Brain-type fatty acid-binding protein 7 (FABP7) is expressed in the adult rodent brain, especially in astrocytes, and has been reported to play a role in astrocyte function in various types of brain damage; however, its role after SCI has not been well studied. In this study, the authors evaluated the expression change of FABP7 after SCI using a mouse spinal cord compression model and observed the effect of FABP7 gene knockout on neuronal damage and functional recovery after SCI. Female FABP7 knockout (KO) mice with a C57BL/6 background and their respective wild-type littermates were subjected to SCI with a vascular clip. The expression of FABP7, neuronal injury, and functional recovery after SCI were analyzed in both groups of mice. Western blot analysis revealed upregulation of FABP7 in the wild-type mice, which reached its peak 14 days after SCI, with a significant difference in comparison to the control mice. Immunohistochemistry also showed upregulation of FABP7 at the same time points, mainly in proliferative astrocytes. The number of surviving ventral neurons in the FABP7-KO mice at 28 days after SCI was significantly lower than that observed in the wild-type mice. In addition, motor functional recovery in the FABP7-KO mice was significantly worse than that of the wild-type mice. The findings of this study indicate that FABP7 could have a neuroprotective role that might be associated with modulation of astrocytes after SCI. FABP7 could potentially be a therapeutic target in the treatment of SCI.

The association between FABP7 serum levels with survival and neurological complications in acetaminophen-induced acute liver failure: a nested case\u2013control study

BackgroundAcetaminophen (APAP)-induced acute liver failure (ALF) is associated with significant mortality due to intracranial hypertension (ICH), a result of cerebral edema (CE) and astrocyte swelling. Brain-type fatty acid-binding protein (FABP7) is a small (15 kDa) cytoplasmic protein abundantly expressed in astrocytes. The aim of this study was to determine whether serum FABP7 levels early (day 1) or late (days 3–5) level were associated with 21-day mortality and/or the presence of ICH/CE in APAP-ALF patients.MethodsSerum samples from 198 APAP-ALF patients (nested case–control study with 99 survivors and 99 non-survivors) were analyzed by ELISA methods and assessed with clinical data from the US Acute Liver Failure Study Group (ALFSG) Registry (1998–2014).ResultsAPAP-ALF survivors had significantly lower serum FABP7 levels on admission (147.9 vs. 316.5 ng/ml, p = 0.0002) and late (87.3 vs. 286.2 ng/ml, p < 0.0001) compared with non-survivors. However, a significant association between 21-day mortality and increased serum FABP7 early [log FABP7 odds ratio (OR) 1.16, p = 0.32] and late (log FABP7 ~ OR 1.34, p = 0.21) was not detected after adjusting for significant covariates (MELD, vasopressor use). Areas under the receiver-operating curve for early and late multivariable models were 0.760 and 0.892, respectively. In a second analysis, patients were grouped based on the presence (n = 46) or absence (n = 104) of ICH/CE. A significant difference in FABP7 levels between patients with or without ICH/CE at early (259.7 vs. 228.2 ng/ml, p = 0.61) and late (223.8 vs. 192.0 ng/ml, p = 0.19) time points was not identified.ConclusionSerum FABP7 levels were significantly elevated at early and late time points in APAP-ALF non-survivors compared to survivors. However, significant differences in FABP7 levels by 21-day mortality were not ascertained after adjusting for significant covariates (reflecting severity of illness). Our study suggests that FABP7 may not discriminate between patients with or without intracranial complications.

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

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.

Brain-Type Fatty Acid Binding Protein (FABP7) and Neurological Complications of Acetaminophen-Induced Acute Liver Failure

Brain-Type Fatty Acid Binding Protein (FABP7) and Neurological Complications of Acetaminophen-Induced Acute Liver Failure

Galantamine therapy for alzheimer’s disease by introducing nanodrug delivery systems

Introduction The major cause of dementia, a major public health problem, is Alzheimer’s disease (AD). A reliable method for the diagnosis and follow up of AD is needed together with a specific biological marker. Galantamine (Gal), an acetylcholinesterase inhibitor for AD therapy, has several reported side effects. Aim of the Work One approach to reduce dosing amounts, frequency of administration, and adverse side effects while maintaining the drug efficiency is the development of drug delivery systems using nanoparticles. Material and Methods Presently, Galantamine with either cerium/calcium hydroxyapatite (Ce/Ca-HAp) or carboxymethyl chitosan/ceria/calcium hydroxyapatite (CMCS/Ce/Ca-HAp) was intraperitoneally injected at a dose of 2.5 mg/kg body weight for 2 and 4 weeks. A total of 86 female adult albino Wistar rats (189–200 g weight) were used. AD was induced in ovariectomized rats with aluminum chloride oral treatment at doses of 17 mg/kg body weight daily for 2 months. The rats were divided into six groups: group 1, which included normal control rats; group 2, which included rats treated with Gal injected intraperitoneally at a dose of 2.5 mg/kg body weight; group 3, which included rats with AD; group 4, which included AD-induced rats treated intraperitoneally with Gal; group 5, which included AD-induced rats treated with Gal coated with Ce/Ca-HAp; group 6, which included AD-induced rats treated with Gal coated with CMCS/Ce/Ca-HAp for 2 and 4 weeks. Results In the current study, AD-induced histological alterations manifested as amyloid plaque formation of different sizes, congestion with perivascular edema, degenerated neurons with diffused gliosis, loss of pyramidal cells, separation of cortical tissue, and formation of fibrous glial scar. Several tests may be cumulatively used for early detection as decreased acetylcholine, B-cell lymphoma 2, tissue thromboplastin, GSH, superoxide dismutase, CAT, and cytochrome P450 and increased amyloid β, Chol, brain-type fatty acid binding protein, nitric oxide, MDA, and GSSH. Treatment with Gal coated with Ce/Ca-HAp imposed a highly significant improvement to near-to-normal levels in both histological and biochemical parameters. Gal coated with CMCS/Ce/Ca-HAp failed to encounter obvious ameliorations. Conclusion In conclusion, brain markers (acetylcholine, B-cell lymphoma 2, amyloid β, tissue thromboplastin, Chol, brain-type fatty acid binding protein, nitric oxide, and MDA) together with brain antioxidants (GSH, superoxide dismutase, CAT, and cytochrome P450) may be used in progressive laboratory testing method besides well-known imaging techniques. Gal therapy may impose limited improvements; thus, drug delivery systems using Gal coated with Ce/Ca-HAp may aid in minimizing dosing amounts, frequency of administration, and adverse side effects of drug while increasing its therapeutic efficacy.

Immunohistochemical analysis of sustentacular cells in the adrenal medulla, carotid body and sympathetic ganglion of mice using an antibody against brain-type fatty acid binding protein (B-FABP).

Little attention has been paid to adrenal sustentacular cells, and several major histology textbooks do not even describe them. This study presents a detailed morphological description of sustentacular cells using immuno-light microscopy and an antibody against brain-type fatty acid-binding protein. The immunopositive sustentacular cells and processes formed lattices with holes of various sizes and compactnesses or openness. In addition, weakly immunostained sheet-like structures with ill-defined contours were often associated with the processes and lattices. In the carotid body, which has traditionally been classified under the name of paraganglia in common with the adrenal medulla, immunostained sustentacular cell processes formed lattices in association with the weakly immunostained sheet-like structures, but the lattices with sheets were more compact and rigid than the adrenal medulla, and appeared like individually distinct compartments. In the ganglion, the immunostained satellite cell processes with the sheets tightly enclosed individual neurons. As a result, the immunostained sheet-like structures were regarded as en-face views of thinly flattened sustentacular cytoplasmic envelopes partially covering the chromaffin cells in the adrenal medulla, and widely in the carotid body in a way rather similar to the satellite cells in the ganglion. In brief, the terminal enclosing portions of adrenal sustentacular cell processes, in cut-views, were too thin/flat to be recognized as distinct lines in immuno-light microscopy because of its resolution limit. They are recognized in en-face views as entities of a substantially spacious extension in immuno-light microscopy.

Abstract 11002: Anemia Plays a Role in Pre-Clinical Myocardial Damage and Cardiovascular Mortality in General Population

Background: Anemia is an independent risk factor for morbidity and mortality in patients with cardiovascular disease. However, the impact of anemia on pre-clinical cardiac damage has not yet fully determined in apparently healthy subjects. The aim of the present study was to investigate whether anemia is associated with pre-clinical cardiac damage and cardiovascular mortality in general population. Methods and Results: A cohort study was conducted with subjects who participated in a community-based annual health check in Takahata, Japan, from 2004 through 2006. We examined blood count, serum levels of brain-type natriuretic peptide (BNP) and heart-type fatty acid binding protein (H-FABP) in participants and prospectively followed them (n = 3,509). Anemia was defined as hemoglobin &lt; 13 g/dl for men; &lt; 12 g/dl for women. Four hundred subjects (11.4%) had anemia. In both gender, BNP levels were higher in subjects with anemia than in those without. H-FABP levels were also higher in male subjects with anemia than in those without, while anemia was not associated with H-FABP levels in female subjects. During follow-up period of 7 years, 40 subjects died of cardiovascular diseases. Kaplan-Meier analysis demonstrated that subjects with anemia had higher cardiovascular mortality than those without. Further, subjects those with macrocytic anemia, defined as anemia with mean corpuscular volume (MCV) ≥ 100 fl, had the highest levels of BNP and H-FABP and the highest event rate among subjects with anemia. Multivariate Cox proportional hazard analysis revealed that anemia was an independent predictor of cardiovascular diseases after adjusting age, gender, smoking index, estimated glomerular filtration rate, and BNP (HR: 2.307; 95% CI, 1.032 - 4.808). Conclusions: Anemia, especially macrocytic anemia, was associated with pre-clinical myocardial damage and cardiovascular mortality in general population.

Characterization of the Atlantic salmon (Salmo salar) brain-type fatty acid binding protein (fabp7) genes reveals the fates of teleost fabp7 genes following whole genome duplications

Whole genome duplications (WGDs) are considered to have been a driving force in the generation of evolutionary diversity that is characteristic of higher eukaryotes. The ancestor of salmonids underwent two additional WGDs compared to mammals, one (3R) at the base of the teleost radiation and another (4R) in the common ancestor of extant salmonids. We have chosen the fatty acid binding protein (fabp) gene family as a model to study the fate of duplicated genes in teleosts following WGDs. As previously described for zebrafish, we identified two copies (fabp7a and fabp7b) of the brain-type fabp gene in several fish including rainbow smelt, but there was only a single transcript in northern pike, the closest relative of the salmonids, and two rather than the expected four fabp7 genes in Atlantic salmon, rainbow trout and grayling. A phylogenetic analysis revealed that a loss of the fabp7a gene occurred in the common ancestor of the northern pike and salmonids after it had diverged from the rainbow smelt, and that the 4R WGD then gave rise to the fabp7bI and fabp7bII observed in salmonids. This is supported by genetic mapping that placed the Atlantic salmon duplicated fabp7b genes on homeologous chromosomes. There was no evidence of neo-functionalization in the salmonid fabp7bI and fabp7bII genes based on dN/dS ratios and an examination of amino acid substitutions. Atlantic salmon fabp7bI and fabp7bII genes are both expressed broadly like fabp7b expression in northern pike. However, only Atlantic salmon fabp7bII, like its counterpart in northern pike and zebrafish, was expressed in the liver. A comparison of ~2000bp upstream of Atlantic salmon fabp7b gene duplicates revealed an insertion of 62bp in fabp7bI relative to fabp7bII. The presence of predicted transcription factor binding sites in this insertion sequence may explain the differential expression of the fabp7b gene duplicates in Atlantic salmon liver.

Candidates for Tumor Markers of Cervical Cancer Discovered by Proteomic Analysis

Cervical cancer is the second most common gynecological cancer among Korean women. While nationwide screening program has developed, the pathogenesis of cervical cancer is unknown. The aim of this study was to compare the protein expression profiles between cervical squamous carcinomas and normal cervical tissues in order to identify proteins that are related to the cancer. Three cervical cancer tissue samples and three normal cervical tissue samples were obtained and protein expression was compared and was identified in the samples with the use of matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). A total of 20 proteins that showed up-regulated expression in the cervical cancer tissue samples were selected and identified. Seven proteins were matched to allograft inflammatory factor 1 (AIF-1), actine-like protein 2 (ALP2), brain type fatty acid-binding protein (B-FABP), NCK adaptor protein 1 (NCK-1), islet cell autoantigen 1 (ICA69), cationic trypsinogen (PRSS1), and cyclin-dependent kinase 4 (CDK4), but the remaining 13 proteins were unidentifiable. After confirmation by RT-PCR, Western blotting and immunohistochemistry, we found that B-FABP, NCK-1, and CDK4 were related to the pathogenesis of cervical cancer. These proteins are suggested as candidates of new pathological tumor markers for cervical cancer.

FABP7 expression in normal and stab-injured brain cortex and its role in astrocyte proliferation

Reactive gliosis, in which astrocytes as well as other types of glial cells undergo massive proliferation, is a common hallmark of all brain pathologies. Brain-type fatty acid-binding protein (FABP7) is abundantly expressed in neural stem cells and astrocytes of developing brain, suggesting its role in differentiation and/or proliferation of glial cells through regulation of lipid metabolism and/or signaling. However, the role of FABP7 in proliferation of glial cells during reactive gliosis is unknown. In this study, we examined the expression of FABP7 in mouse cortical stab injury model and also the phenotype of FABP7-KO mice in glial cell proliferation. Western blotting showed that FABP7 expression was increased significantly in the injured cortex compared with the contralateral side. By immunohistochemistry, FABP7 was localized to GFAP+ astrocytes (21% of FABP7+ cells) and NG2+ oligodendrocyte progenitor cells (62%) in the normal cortex. In the injured cortex there was no change in the population of FABP7+/NG2+ cells, while there was a significant increase in FABP7+/GFAP+ cells. In the stab-injured cortex of FABP7-KO mice there was decrease in the total number of reactive astrocytes and in the number of BrdU+ astrocytes compared with wild-type mice. Primary cultured astrocytes from FABP7-KO mice also showed a significant decrease in proliferation and omega-3 fatty acid incorporation compared with wild-type astrocytes. Overall, these data suggest that FABP7 is involved in the proliferation of astrocytes by controlling cellular fatty acid homeostasis.Electronic supplementary materialThe online version of this article (doi:10.1007/s00418-011-0865-4) contains supplementary material, which is available to authorized users.

Importance of brain‑type fatty acid binding protein for cell-biological processes in human renal carcinoma cells

The molecular mechanisms underlying renal cell carcinoma (RCC) development and progression are still not completely understood. The importance of fatty acid binding proteins (FABP) for the progression of carcinomas has been shown for several tumors. However, the importance of brain-type FABP (B‑FABP) in cell-biological processes in renal carcinoma cells is unknown. Therefore, it was the aim of this study to evaluate the role of B‑FABP in processes such as proliferation, migration and invasion. By using the approach of down- and up-regulation of B‑FABP in human kidney carcinoma cells Caki‑2 and Caki‑1, the potential participation of B‑FABP in proliferation, migration and invasion was demonstrated. B‑FABP was down-regulated at both mRNA and protein levels following treatment of Caki‑2 cells with B‑FABP siRNA. Down-regulation of B‑FABP decreased cell proliferation and migration but did not affect invasion. The transfection of Caki‑1 cells with human B‑FABP cDNA generated an increment of B‑FABP mRNA but the protein was not detectable. Transfected Caki‑1 cells developed a faster proliferation compared to untreated cells. An effect on the process of invasion was not observed. Our data suggest that B‑FABP is involved in cell proliferation and migration of human renal carcinoma cells. The detailed molecular mechanisms remain to be elucidated.

Fatty-Acid Binding Proteins Modulate Sleep and Enhance Long-Term Memory Consolidation in Drosophila

Sleep is thought to be important for memory consolidation, since sleep deprivation has been shown to interfere with memory processing. However, the effects of augmenting sleep on memory formation are not well known, and testing the role of sleep in memory enhancement has been limited to pharmacological and behavioral approaches. Here we test the effect of overexpressing the brain-type fatty acid binding protein (Fabp7) on sleep and long-term memory (LTM) formation in Drosophila melanogaster. Transgenic flies carrying the murine Fabp7 or the Drosophila homologue dFabp had reduced baseline sleep but normal LTM, while Fabp induction produced increases in both net sleep and LTM. We also define a post-training consolidation “window” that is sufficient for the observed Fabp-mediated memory enhancement. Since Fabp overexpression increases consolidated daytime sleep bouts, these data support a role for longer naps in improving memory and provide a novel role for lipid-binding proteins in regulating memory consolidation concurrently with changes in behavioral state.