Disease relevance of GFAP

• To investigate the function of GFAP, we have studied the human astrocytoma cell line, U251, which constitutively expresses GFAP and vimentin in the same 10-nm filaments [1].
• GFAP was detectable in cultures derived from malignant Grade IV astrocytomas and its expression was stable during the course of the study [2].
• The astrocytoma, neuroblastoma, and oligodendroglioma cell lines expressed only GFAP, NF-M, and cytokeratin K7, respectively [3].
• Alexander disease (AxD) is a rare but fatal neurological disorder caused by mutations in the astrocyte-specific intermediate filament protein glial fibrillary acidic protein (GFAP) [4].
• Chondrosarcomas showed strong vimentin positivity, whereas ependymomas were positive for GFAP [5].

Psychiatry related information on GFAP

• Serum anti-GFAP and anti-S100 autoantibodies in brain aging, Alzheimer's disease and vascular dementia [6].
• Significantly increased glial fibrillary acidic protein (GFAP) expression was seen in postmortem brain tissue from demented patients with Alzheimer's disease (AD) (73 cases, 61 females/12 males, mean age 84 +/- 9 years) compared to controls (22 cases, 10 females/12 males, mean age 78 +/- 9 years) [7].
• When patients with schizophrenia were divided into demented and non-demented subtypes, those with dementia demonstrated significantly greater numbers of GFAP-positive astrocytes than those without dementia [8].
• GFAP levels in children with infantile autism were higher than those in normal children of the same age range [9].
• In the white matter of ACC we detected a significant effect of diagnosis (P<0.04) with GFAP mRNA levels decreased in individuals with schizophrenia and bipolar disorder as compared with normal controls [10].

High impact information on GFAP

• We previously found that overexpression of human GFAP in astrocytes of transgenic mice is fatal and accompanied by the presence of inclusion bodies indistinguishable from human Rosenthal fibers [11].
• The pathological hallmark of all forms of Alexander disease is the presence of Rosenthal fibers, cytoplasmic inclusions in astrocytes that contain the intermediate filament protein GFAP in association with small heat-shock proteins [11].
• These results suggested that a primary alteration in GFAP may be responsible for Alexander disease [11].
• Pancreatic islets of Langerhans are enveloped by peri-islet Schwann cells (pSC), which express glial fibrillary acidic protein (GFAP) and S100beta. pSC-autoreactive T- and B-cell responses arise in 3- to 4-week-old diabetes-prone non-obese diabetic (NOD) mice, followed by progressive pSC destruction before detectable beta-cell death [12].
• The gfa gene encodes glial fibrillary acidic protein, an intermediate filament protein expressed in glial cells [13].

Chemical compound and disease context of GFAP

• p16(ink4a) and retinoic acid modulate rhoA and GFAP expression during induction of a stellate phenotype in U343 MG-A astrocytoma cells [14].
• Both effective and ineffective agents in rat cultures were tested for their ability to stimulate release of thromboxane from these gliomas, and also from cultures of medulloblastoma and ependymoma which contained significant numbers of GFAP-positive cells [15].
• Ten hemangioblastomas of the central nervous system were examined by an immunoperoxidase technique for glial fibrillary acidic protein (GFAP), S-100 protein, and Factor VIII-related antigen to determine the origin of the stromal cells [16].
• As a feasibility study, we isolated a C6 rat glioma cell line stably transfected with a lacZ reporter gene driven by the gfa2 human GFAP promoter fragment [17].
• Therefore, the FS cell adenoma is characterized by S-100- and GFAP-positive FS cells and PAS-positive follicles [18].

Biological context of GFAP

• Two stable antisense cell lines from separate transfections were isolated and were shown to be GFAP negative by Northern and Western blot analyses, and by immunofluorescence studies [1].
• These cells respond to neurons in vitro in the same way as primary astrocytes: they withdraw from the cell cycle, support neuronal cell survival and neurite outgrowth, and they extend complex, GFAP-positive processes [1].
• In astrocytes we studied the phosphorylation of the two major cytoskeletal proteins, vimentin and GFAP, which is normally stimulated by isoproterenol, and found that gp120 partially (40-50%) prevented such stimulation [19].
• This regulation of GFAP assembly contributes to extensive remodeling of glial frameworks in mitosis [20].
• Isoform GFAPepsilon, produced by alternative splicing of the GFAP gene, includes a new tail domain that confers a presenilin binding capacity [21].

Anatomical context of GFAP

• These data support the conclusion that the glial-specific intermediate filament protein, GFAP, is required for the formation of stable astrocytic processes in response to neurons [1].
• Most importantly, PCNA+ cells were shown to coexpress beta III-tubulin or GFAP, demonstrating the generation of neurons and glial cells in the SEL of the diseased human brain [22].
• In addition, at all CMT1A disease stages analysed, LNGF-R-positive Schwann cells were glial fibrillary acidic protein (GFAP) negative [23].
• A much higher proportion of total GFAP was found in the Triton X-insoluble fraction of plectin-deficient fibroblasts than in wild-type fibroblasts [4].
• The number of chondrocytes showing GFAP immunoreactivity decreased from fetal life to adulthood [24].

Associations of GFAP with chemical compounds

• Treatment of cells with an inhibitor of guanine nucleotide biosynthesis, mycophenolic acid, enhanced detection of GFAP by indirect immunofluorescence microscopy [2].
• GFAP binds integrin alphavbeta8, which initiates mitotic signals soon after damage by interacting with fibrin [25].
• Patients with Alzheimer disease exhibited a significant decrease in vasopressin (9.75 vs 16.7, p < 0.001) and neurotensin (6.82 vs 9.63, p < 0.002) neurons, as well as a corresponding increase in the GFAP-stained astrocyte/Nissl-stained neuron ratio (0.54 vs 0.10, p < 0.009) [26].
• Immunohistochemical staining for GFAP complements the reticulin stain in confirming the presence of two cell populations in GS [27].
• All-trans-retinoic acid (RA) induction caused the BDNF-MSCs to differentiate into neural cells with significantly increased expressions of such neural-specific proteins as nestin, NeuN, O4, and glial fibrillary acidic protein (GFAP) [28].

Physical interactions of GFAP

• (1994) who have shown that AP-1 DNA binding activity in hippocampus recognized an AP-1 sequence from the promoter region of the GFAP which is a potential target gene. van de Klundert et al [29].
• We have previously reported that a particular cytosine residue within a STAT3-binding site in the astrocyte-specific marker glial fibrillary acidic protein (GFAP) gene promoter becomes demethylated in neuroepithelial cells as gestation proceeds [30].
• The MEN1 gene product interacts with glial fibrillary acidic protein (GFAP) in the brain [31].
• In MPTP-treated marmosets BDNF caused increased ipsilateral striatal [3H]mazindol binding with increased somatic size and staining intensity in GAD-immunoreactive cells and a 10-20% loss of nigral TH-immunoreactive cells with increased GFAP staining [32].
• The functionality of an estrogen response element in the 5'-upstream region of the GFAP promoter was established by site-directed mutagenesis and binding of human recombinant estrogen receptor in gel shift assays [33].

Co-localisations of GFAP

• In epiretinal membranes of patients with PVR, HB-EGF immunoreactivity partially colocalized with GFAP [34].
• Immunocytochemical double labeling revealed that both anti-iNOS immunoreactivity and anti-IL-1beta immunoreactivity colocalized with glial fibrillary acidic protein immunoreactivity in GBM [35].
• In addition, caveolin-1 was co-localized in hypertrophied GFAP-positive astrocytes [36].

Regulatory relationships of GFAP

• Administration of S100B before TMT treatment prevented TMT-induced changes in morphology and GFAP expression [37].
• Vimentin was demonstrated in four cases and was not always co-expressed with GFAP [38].
• Our results demonstrate that not only the extent of AD lesions and GFAP expression, but also the relationship between AD lesions and the GFAP expression is influenced by the ApoE epsilon4 allele [7].
• AQP1 was localized to the same cell population expressing glial fibrillary acidic protein (GFAP), but not to the neurons in the plexuses, indicating glial cell-specific expression [39].
• Plectin regulates the organization of glial fibrillary acidic protein in Alexander disease [4].

Other interactions of GFAP

• These studies revealed a strong expression of GFAP, vimentin, and CD34 [40].
• There was a correlation between GFAP levels and ambulation in SP multiple sclerosis (r = 0.57, P < 0.01), and between S100B level and the 9HPT in PP multiple sclerosis patients (r = -0.85, P < 0.01) [41].
• RPE cells in culture also expressed CK-Vim-GFAP and changed from an epithelial shape to a migratory fibroblast/fusiform-shaped phenotype in the presence of subretinal fluid aspirates and pathologic vitreous from proliferative intraocular disorders [42].
• RESULTS: Based on morphology and on GFAP and vimentin immunopositivity, retinas from all subjects with diabetes immunostained strongly to VEGF in elongated processes that appeared to be Müller cells [43].
• 2. Neurofilament protein could not be demonstrated in fixed material, and all tumors were negative for GFAP and desmin [44].

Analytical, diagnostic and therapeutic context of GFAP

• Immunoblots provided the most sensitive method for monitoring GFAP expression and showed the limitations of using immunofluorescence detection methods [2].
• Expression of glial fibrillary acidic protein (GFAP) was assayed in 11 glioma-derived cell cultures [2].
• Co-localization, co-immunoprecipitation, and in vitro overlay analyses demonstrated direct interaction of plectin and GFAP [4].
• The relative amounts of GFAP present in infected and uninfected U-251 cells were quantified by image analysis of data sets obtained by confocal microscopy by using vimentin, another intermediate filament on which MVeGFP has no effect, as a control [45].
• Donor cells identified with an antibody to human nuclei or human-specific DNA in situ hybridization maintained expression of their original marker antigens and showed no expression of the neural markers MAP2 and NeuN (neurons), GFAP (astrocytes), and CNP (oligodendrocytes) [46].

References