Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immediate early gene (IEG) products, such as FOS and JUN, may partially mediate the long-term transcriptional response of CNS cells to specific changes in their environment. To determine whether IEG products might be involved in the immature brain's response to hypoxia-ischemia (H-I), 7-day-old rat pups were subjected to unilateral common carotid artery ligation followed by 3 h of hypoxia (8% O2/92% N2) at 37 degrees C, which results in pathological changes only in specific regions of the hemisphere ipsilateral to ligation. Time course experiments were performed, in which animals were sacrificed between 1 and 24 h after H-I. RNAs from several brain regions were analyzed by Northern blot hybridization for their relative concentrations of nine IEG mRNAs (c-fos, c-jun, junB, TIS 1 (nur77), TIS7, TIS8 (zif268), TIS10, TIS11, and TIS21). Induction of all IEGs, except TIS7 and TIS10, was observed in ipsilateral forebrain, and, less frequently, in contralateral forebrain, at 1, 2, and 3 h post-hypoxia. In some animals, lower levels of expression were also detected at 4, 18 and 24 h. With minor exceptions, co-induction of all seven IEGs was observed in a given RNA sample. Induction of two other mRNAs, representing the heat shock and astrocytic responses, were also observed. Hsp70 mRNA levels were increased only in the brains of animals exhibiting IEG induction. However, hsp70 induction was confined to the ipsilateral forebrain, implying a more direct relationship between its expression and permanent morphological damage. GFAP mRNA induction occurred predominantly in ipsilateral forebrain samples at 18 and 24 h post-hypoxia. Levels of B-actin and ubiquitin mRNAs were relatively constant in the same RNA samples. In control experiments c-fos mRNA induction was not detected after sham ligation with hypoxia, ligation with sham hypoxia, or hypoxia alone. These results suggest that the immature brain is highly responsive to H-I at the level of gene expression, involving at least three different rapid response systems.
Brain Res Mol Brain Res 1993 May
PMID:Immediate early gene induction after neonatal hypoxia-ischemia. 768 83

We investigated the effect of beraprost sodium (BPS), a new prostacyclin analog, and dizocilpine (MK-801) on repeated ischemia-induced cerebral atrophy and chronic cortical neuronal loss in gerbils. The left common carotid artery of gerbils was repeatedly occluded (for 10, 7, 7, and 7 min) at intervals of 24 h. The thickness of the cerebral cortex of the ischemic hemisphere diminished with increasing time of reperfusion after an ischemic insult. The animals were given BPS (1-100 micrograms/kg, po) or MK-801 (3-300 micrograms/kg, sc) after the first ischemic insult, and then twice daily for 4 wk. Increases in the amount of neuronal loss and acidophilic neurons, and progressive atrophy were observed with increasing time of reperfusion in the cerebral cortex of the ischemic hemisphere. Cortical sections revealed no astrocytes positive for glial fibrillary acidic protein (GFAP), whereas the hippocampal CA1 area showed neuronal loss accompanied by GFAP-positive astrocytes. In control animals at 4 wk survival, the area ratio (area of ischemic cortex/area of opposite cortex) and the cortical neurons ratio (number of neurons in ischemic cortex/number of neurons in opposite cortex) were 89.8 +/- 3.0% and 74.6 +/- 3.4%, respectively. BPS was found to inhibit atrophy and chronic cortical neuronal loss in the ischemic hemisphere in a dose-dependent manner, whereas MK-801 showed no inhibitory effects at any dose tested. These results may suggest that the nature of neuronal degeneration differs between the cortical and hippocampal areas, that cortical neuronal degeneration might not involve glutamate pathways with NMDA receptors in this model, and that prostacyclin could play an essential role in prevention of ischemia-induced progressive neuronal loss.
Mol Chem Neuropathol
PMID:Effect of beraprost sodium (BPS), a prostacyclin analog, and dizocilpine (MK-801) on repeated ischemia-induced chronic cortical atrophy in gerbils. 770 5

Numbers of astrocytes immunoreactive for glial fibrillary acidic protein (GFAP) are markedly increased in the mediobasal hypothalamus (MBH) of adult hypogonadal (hpg) mice. The astrocytosis cannot be reversed by administration of gonadal steroids. To investigate whether the glial changes are established in the perinatal period, when crucial developments occur in rodent brain, we determined the distribution of GFAP-IR astrocytes in normal and hpg mouse brain from birth to adulthood. The period up to 3 weeks of age was characterized by the gradual disappearance of radial glia and the increase in mature astrocytes in some brain regions, for example hippocampus. However, there were no apparent differences in GFAP-IR elements between normal and hpg brains and very few astrocytes in the MBH. From age 1 month, increased numbers of GFAP-IR astrocytes were apparent in the hypothalamus in hpg mice and this difference was more obvious at 2 months. By 4 months of age the characteristic astrocytosis in the MBH had been attained and this did not change in older hpg mice. These observations provide no evidence for upregulation of the GFAP gene during the first 2 postnatal weeks when its transcription is highest and astrocytes are proliferating most rapidly. It is more likely that the astrocyte response in the MBH in hpg mice reflects permanent differences in steroid-induced neuronal connectivity, caused by the hypogonadism.
Mol Cell Neurosci 1994 Dec
PMID:The development of astrocytes immunoreactive for glial fibrillary acidic protein in the mediobasal hypothalamus of hypogonadal mice. 770 37

Axonal sprouting and synaptic reorganization play an important role in the adaptation of the CNS to injury. However, the molecular mechanisms underlying this neuronal plasticity are poorly understood. In the present study we used in situ hybridization to examine the expression of NCAM mRNA in normal hippocampus, and in response to entorhinal cortex (EC) lesions and transient global ischemia. Both neurons and astrocytes were labeled by digoxygenin-tagged cRNA probes which recognize all three major NCAM isoforms of the adult CNS. In contrast, NCAM180-specific probes labeled only neurons in the hippocampus. After unilateral EC lesion, a transient and anatomically restricted upregulation of NCAM120/140 mRNA in reactive astrocytes in the denervated molecular layer of the dentate gyrus was observed. This increase was only present 2-4 days after the lesion whereas the GFAP mRNA increase was present up to 30 days postlesion. Following global ischemia a similar, transient increase of NCAM120/140 mRNA labeling of reactive astrocytes was observed; this increase was anatomically restricted to CA1, where neuronal loss occurred. Results suggest that the transient upregulation of NCAM120/140 mRNA in reactive astrocytes shortly after injury might be an important molecular mechanism in the cascade of events underlying neuronal plasticity in the adult CNS.
Brain Res Mol Brain Res 1995 Jan
PMID:Transient upregulation of NCAM mRNA in astrocytes in response to entorhinal cortex lesions and ischemia. 770 69

Previous studies have revealed that kindled seizures induced via chronically implanted electrodes up-regulate the expression of glial fibrillary acidic protein (GFAP), the protein constituent of intermediate filaments in astrocytes. The present study evaluates the consequences of a single electroconvulsive seizure (ECS) on glial gene expression. ECS were induced in mice via externally-placed electrodes. GFAP mRNA levels were evaluated 1, 2, 4, and 6 days post-seizure by in situ hybridization. GFA immunocytostaining was evaluated in a separate series of animals. Following a single ECS, the levels of mRNA for GFAP increased several fold by 1 day and were still substantially elevated at 4 days. The increases occurred primarily in the dentate gyrus despite the fact that the seizures involved widespread brain regions. GFAP mRNA levels were also increased in areas bordering the ventricles, especially in areas immediately adjacent to the dentate gyrus. These results indicate that ECS up-regulates the mRNA for a key structural protein of astrocytes in a manner that is similar to the response that occurs following injury, that this response occurs selectively in a part of the brain that plays a key role in memory function, and that the increase may be due in part to a diffusible substance that also affects glial gene expression in nearby structures.
Brain Res Mol Brain Res 1994 Sep
PMID:Electroconvulsive seizures upregulate astroglial gene expression selectively in the dentate gyrus. 780 20

In adult rats, the expression of transcription factor proteins c-Jun and CREB and their colocalization with tyrosine hydroxylase (TH) were investigated in neurons of the substantia nigra compacta (SNC) axotomized by stereotaxic unilateral transection of the medial forebrain bundle (MFB). Axotomized SNC neurons were identified by injection of the retrograde tracer horseradish-peroxidase-coupled-gold (HRP-gold) into the ipsilateral striatum 5 days prior to MFB transection. Nuclear c-Jun immunoreactivity (IR) appeared 36 h after MFB transection in SNC neurons, was maximal after 5 days, and declined after 10 days. c-Jun-IR was visible in HRP-gold-labeled SNC neurons, demonstrating that c-Jun is in fact expressed in axotomized neurons. The constitutively expressed CREB (calcium/cAMP response element-binding protein, syn. CREB-1) was present in apparently all neuronal and glial cells in the brains of untreated rats including those SNC neurons that coexpressed TH. Three days following MFB transection, the nuclear CREB-IR disappeared in the axotomized SNC neurons labeled by TH-IR and was almost completely absent after 20 days in this neuronal population. The TH-IR rapidly declined 5 days after MFB transection, and 10 and 100 days post-axotomy the number of TH-labeled neurons was reduced by 52 and 80%, respectively. During this period, the majority of surviving TH positive neurons coexpressed c-Jun but were immunonegative for CREB. Between 3 and 60 days following MFB transection, the number of CREB-labeled glial cell nuclei increased in the ipsilateral substantia nigra by about 80%. Concomitantly, expression of GFAP, a marker protein for astrocytes, was also enhanced whereas nuclear c-Jun-, JunD-, and c-Fos-IR did not change in glial cells. These findings demonstrate that c-Jun can be expressed in axotomized neurons during the absence of CREB and suggest a role of c-Jun in the transcriptional control of the TH gene.
Mol Cell Neurosci 1994 Oct
PMID:Induction of c-Jun and suppression of CREB transcription factor proteins in axotomized neurons of substantia nigra and covariation with tyrosine hydroxylase. 782 Mar 66

1. We have previously shown that acute exposure to the HIV coat protein gp120 interferes with the beta-adrenergic regulation of astroglial and microglial cells (Levi et al., 1993). In particular, exposure to 100 pM gp120 for 30 min depressed the phosphorylation of vimentin and glial fibrillary acidic protein (GFAP) induced by isoproterenol in rat cortical astrocyte cultures. In the present study we have extended our analysis on the effects of gp120 on astroglial protein phosphorylation. 2. We found that chronic (3-day) treatment of the cells with 100 pM gp120 before exposure to isoproterenol was substantially more effective than acute treatment in depressing the stimulatory effect of the beta-adrenergic agonist on vimentin and GFAP phosphorylation. 3. Even after chronic treatment with gp120, no differences were found in the levels and solubility of these proteins. 4. Besides stimulating the phosphorylation of intermediate filament proteins, isoproterenol inhibited the incorporation of 32P into a soluble acidic protein of 80,000 M(r), which was only minimally present in Triton X-100-insoluble extracts. 5. Treatment of astrocytes with a phorbol ester or exposure to 3H-myristic acid indicated that the acidic 80,000 M(r) protein is a substrate for protein kinase C (PKC) and is myristoylated, thus suggesting that it is related to the MARCKS family of PKC substrates. 6. Acute (30-min) treatment with 100 pM gp120 totally prevented the inhibitory effect of isoproterenol on the phosphorylation of the 80,000 M(r) MARCKS-like protein. 7. Our studies corroborate the hypothesis that viral components may contribute to the neuropathological changes observed in AIDS through the alteration of signal transduction systems in glial cells.
Cell Mol Neurobiol 1994 Apr
PMID:Human immunodeficiency virus protein gp120 interferes with beta-adrenergic receptor-mediated protein phosphorylation in cultured rat cortical astrocytes. 784 74

We have investigated the role of serotonergic neurons on the astrocytes catabolism of glutamate by analyzing glutamine synthetase (GS) and glutamate dehydrogenase (GDH) expression in the hippocampus after the degeneration of serotonergic neurons by a specific neurotoxin (5,7-DHT). 5,7-DHT caused reactive gliosis with hypertrophy (increase in glial fibrillary acidic protein (GFAP) expression) but not proliferation of astrocytes. Glutamate metabolism appeared preferentially regulated by a control of GDH expression rather than GS since the expression of GDH was specifically and significantly induced in the hippocampus whereas the level of GS remained unchanged. The inhibition of serotonin synthesis (by para-chlorophenylalanine (p-CPA) administration) produced no significant increase of GDH level. This suggests that serotonin is not the principal factor involved in this control of GDH expression.
Brain Res Mol Brain Res 1994 Oct
PMID:Modifications of glial metabolism of glutamate after serotonergic neuron degeneration in the hippocampus of the rat. 785 35

Haloperidol, a dopamine receptor antagonist clinically used as an antipsychotic drug, induces long-term deleterious effects in offspring development when administered prenatally. However, the basis for this overall response to the drug remains unknown. Here we describe that prenatal administration of haloperidol in rats induces a drastic and selective reduction in the expression of plasticity-related genes in neonate forebrain, but not in mesencephalon. GABAergic and enkephalinergic markers such as glutamic acid decarboxylase activity and mRNA, and preproenkephalin mRNA were also diminished in forebrain. However, the expression of other genes such as epidermal growth factor-receptor, glial fibrillary acidic protein, and several proto-oncogenes (src, fos and myc), and a cholinergic marker such as choline acetyltransferase activity were unaltered. In addition, haloperidol promoted a significant decrease in mitotic cell number and cellular density in the striatum, one of the forebrain regions with the highest dopamine receptor density. These findings suggest that prenatal dopamine receptor occupancy may be a critical factor in controlling the development of forebrain target cells through mechanisms involving changes in the expression of plasticity-related genes.
Brain Res Mol Brain Res 1994 Oct
PMID:Prenatal haloperidol induces a selective reduction in the expression of plasticity-related genes in neonate rat forebrain. 785 69

The unique structures of process-bearing cells in the central nervous system (CNS) present an ideal model with which to study the differential distribution of mRNA. We conducted a side-by-side examination of the intracellular distribution of nine neural mRNAs by in situ hybridization histochemistry in mammalian brain and observed four general types of mRNA distributions. (1) Some mRNA species were confined to cell somas and included those encoding the glial proteins, myelin proteolipid protein and 2'3'-cyclic nucleotide-3'-phosphodiesterase and the neuronal enzymes, neuron-specific enolase and glutamate decarboxylase-67. (2) Some mRNAs were found abundantly within the cell soma and were also located throughout cellular processes. These included myelin basic protein (MBP) mRNA, which was localized to the cell soma and myelin sheaths of oligodendrocytes, and glial fibrillary acidic protein (GFAP) mRNA, which was localized to the cell soma and processes of reactive and some non-reactive astrocytes in the adult brain and radial glia in embryonic brain. (3) Some mRNAs were found primarily in perinuclear cytoplasm but in some cells were also observed in cell processes. These included mRNAs encoding the protein kinase C/calmodulin-binding substrates, RC3 (neurogranin) and GAP-43, which were identified in the somas as well as within the proximal dendritic branches of specific forebrain neurons. (4) Some mRNAs were localized primarily within cell processes. These included MAP2 mRNA, which was identified by deep staining within dendritic fields but by only light staining within neuronal cell bodies. The data also indicated that the stage of cellular development and the regional location of a cell within the CNS had a profound influence on translocation events. MAP2 mRNA was found in the dendritic processes of most neurons but was confined to the soma of neurons in specific brainstem nuclei. MBP mRNA was confined to the perinuclear cytoplasm of immature oligodendrocytes and was then transported into the myelin sheath at a developmental stage corresponding to myelination. The distribution patterns of these mRNAs are likely to reflect the mechanism by which the protein products of these molecules are targeted within neurons and glia. In addition, mRNA movement may be influenced by cellular and regional factors not encoded solely within the structure of the translocated mRNA.
Brain Res Mol Brain Res 1994 Nov
PMID:Cellular influences on RNA sorting in neurons and glia: an in situ hybridization histochemical study. 787 39


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>