Glial Fibrillary Acidic Protein: Dynamic Property and Regulation by Phosphorylation

Inagaki, Masaki; IMakamura, Yu; Takeda, Masatoshi; Nishimura, Tsuyoshi; Inagaki, Naoyuki

doi:10.1111/j.1750-3639.1994.tb00839.x

Cited by 142 publications

(88 citation statements)

References 79 publications

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“…34 Phosphorylation results in the disaggregation of GFAP molecules 35 and results in a protein molecule with a greater negative charge. 36 Spots 311 and 500 may represent phosphorylated forms of the protein.…”

Section: Discussionmentioning

confidence: 99%

Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder

Cd²,

Jp³

et al. 2000

Mol Psychiatry

496

272

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Severe psychiatric disorders such as schizophrenia, bipolar disorder and major depressive disorder are brain diseases of unknown origin. No biological marker has been documented at the pathological, cellular, or molecular level, suggesting that a number of complex but subtle changes underlie these illnesses. We have used proteomic technology to survey postmortem tissue to identify changes linked to the various diseases. Proteomics uses two-dimensional gel electrophoresis and mass spectrometric sequencing of proteins to allow the comparison of subsets of expressed proteins among a large number of samples. This form of analysis was combined with a multivariate statistical model to study changes in protein levels in 89 frontal cortices obtained postmortem from individuals with schizophrenia, bipolar disorder, major depressive disorder, and non-psychiatric controls. We identified eight protein species that display disease-specific alterations in level in the frontal cortex. Six show decreases compared with the non-psychiatric controls for one or more diseases. Four of these are forms of glial fibrillary acidic protein (GFAP), one is dihydropyrimidinase-related protein 2, and the sixth is ubiquinone cytochrome c reductase core protein 1. Two spots, carbonic anhydrase 1 and fructose biphosphate aldolase C, show increase in one or more diseases compared to controls. Proteomic analysis may identify novel pathogenic mechanisms of human neuropsychiatric diseases. Molecular Psychiatry (2000) 5, 142-149.

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Section: Discussionmentioning

confidence: 99%

Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder

Cd²,

Jp³

et al. 2000

Mol Psychiatry

496

272

View full text Add to dashboard Cite

show abstract

“…Enzymes including protein kinase A (PKA), protein kinase C (PKC), calcium/calmodulin dependent protein kinase II (CaMKII), Rho kinase, cleavage furrow (CF) kinase and Cdc2 kinase modulate the phosphorylation of one or more of the GFAP residues [8][9][10][11][12]. Phosphorylation in the N-terminal region (head domain) affects GFAP assembly and in the C-terminal region (tail domain), phosphorylation of Ser-389 affects interactions between GFAP and other intermediate filaments or proteins [10]. Phosphorylation of GFAP causes disassembly of the intermediate filaments and conversely, dephosphorylation (by phosphatase) restores its ability to polymerize [8].…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of GFAP is Associated with Injury in the Neonatal Pig Hypoxic-Ischemic Brain

Sullivan

Miller

et al. 2012

Neurochem Res

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Glial fibrillary acidic protein (GFAP) is an intermediate filament protein expressed in the astrocytecytoskeleton that plays an important role in the structure and function of the cell. GFAP can be phosphorylated at six serine (Ser) or threonine (Thr) residues but little is known about the role of GFAP phosphorylation in physiological and pathophysiological states. We have generated antibodies against two phosphorylated GFAP (pGFAP) proteins: p8GFAP, where GFAP is phosphorylated at Ser-8 and p13GFAP, where GFAP is phosphorylated at Ser-13. We examined p8GFAP and p13GFAP expression in the control neonatal pig brain and at 24h and 72h after an hypoxic-ischemic (HI) insult. Immunohistochemistry demonstrated pGFAP expression in astrocytes with an atypical cytoskeletal morphology, even in control brains. Semi-quantitative western blotting revealed that p8GFAP expression was significantly increased at 24h post-insult in HI animals with seizures in frontal, parietal, temporal and occipital cortices. At 72h post-insult, p8GFAP and p13GFAP expression were significantly increased in HI animals with seizures in brain regions that are vulnerable to cellular damage (cortex and basal ganglia), but no changes were observed in brain regions that are relatively spared following an HI insult (brain stem and cerebellum). Increased pGFAP expression was associated with poor neurological outcomes such as abnormal encephalography (EEG) and neurobehaviour, and increased histological brain damage.Phosphorylation of GFAP may play an important role in astrocyte remodelling during development and disease and could potentially contribute to the plasticity of the central nervous system. 3

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“…11 B, C). To further investigate cell types marked by LCN2 antibody, we labeled spinal cord sections with the anti-GFAP antibody, which is the marker for radial glia (Inagaki et al, 1994), together with the LCN2 antibody. All LCN2 ϩ processes expressed GFAP, indicating that all LCN2 ϩ cells are actually radial glial cells in the spinal cord of zebrafish embryos (Fig.…”

Section: Expression and Functional Analysis Of Lcn2 In Zebrafish Modelmentioning

confidence: 99%

Lipocalin-2 Is an Autocrine Mediator of Reactive Astrocytosis

Lee¹,

Park²,

Lee³

et al. 2009

J. Neurosci.

239

238

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Astrocytes, the most abundant glial cell type in the brain, provide metabolic and trophic support to neurons and modulate synaptic activity. In response to a brain injury, astrocytes proliferate and become hypertrophic with an increased expression of intermediate filament proteins. This process is collectively referred to as reactive astrocytosis. Lipocalin 2 (lcn2) is a member of the lipocalin family that binds to small hydrophobic molecules. We propose that lcn2 is an autocrine mediator of reactive astrocytosis based on the multiple roles of lcn2 in the regulation of cell death, morphology, and migration of astrocytes. lcn2 expression and secretion increased after inflammatory stimulation in cultured astrocytes. Forced expression of lcn2 or treatment with LCN2 protein increased the sensitivity of astrocytes to cytotoxic stimuli. Iron and BIM (Bcl-2-interacting mediator of cell death) proteins were involved in the cytotoxic sensitization process. LCN2 protein induced upregulation of glial fibrillary acidic protein (GFAP), cell migration, and morphological changes similar to characteristic phenotypic changes termed reactive astrocytosis. The lcn2-induced phenotypic changes of astrocytes occurred through a Rho-ROCK (Rho kinase)-GFAP pathway, which was positively regulated by nitric oxide and cGMP. In zebrafishes, forced expression of rat lcn2 gene increased the number and thickness of cellular processes in GFAP-expressing radial glia cells, suggesting that lcn2 expression in glia cells plays an important role in vivo. Our results suggest that lcn2 acts in an autocrine manner to induce cell death sensitization and morphological changes in astrocytes under inflammatory conditions and that these phenotypic changes may be the basis of reactive astrocytosis in vivo.

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Glial Fibrillary Acidic Protein: Dynamic Property and Regulation by Phosphorylation

Cited by 142 publications

References 79 publications

Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder

Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder

Phosphorylation of GFAP is Associated with Injury in the Neonatal Pig Hypoxic-Ischemic Brain

Lipocalin-2 Is an Autocrine Mediator of Reactive Astrocytosis

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