Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.4.37 (CNPase)
539 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The levels of myelin basic protein, proteolipid protein, and 2',3'-cyclic nucleotide 3'-phosphohydrolase (EC 3.1.4.37) in cerebral hemispheres of wild-type, heterozygous jp/+, and hemizygous jp/Y mice of different ages were determined by radioimmunoassay and immunoblotting. In jp/Y brain the level of myelin basic protein was 8% that of wild-type at all ages. All forms of the protein were reduced although the 21.5K Mr form was relatively spared at early ages compared to the 18.5K, 17K, and 14K Mr forms. The level of 2',3'-cyclic nucleotide 3'-phosphohydrolase was 8% that of wild-type at all ages, and proteolipid protein was undetectable at any age. These results are consistent with the hypothesis that the jimpy mutation blocks myelin morphogenesis subsequent to incorporation of 21.5K Mr myelin basic protein but prior to incorporation of proteolipid protein. In jp/+ brain the levels of the three proteins were reduced commensurately to 60-70% those of wild-type. The deficit was apparent as early as 10 days after birth and remained proportionately constant throughout development. These results suggest that in jp/+ mice, X-chromosome inactivation produces a mosaic population of functionally wild-type and functionally jimpy oligodendrocytes. The former elaborate normal amounts of myelin but do not completely compensate for the myelin deficit due to the latter.
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PMID:Effect of the jimpy mutation on expression of myelin proteins in heterozygous and hemizygous mouse brain. 620 39

Primary cultures from newborn rat cerebral cortex, striatum, hippocampus, brainstem and cerebellum were grown for 14 days. There was a linear relationship between the amount of material seeded and the protein content of the respective culture. The amount of tissue material seeded was selected so that the different cultures reached confluence at 6-7 days and contained similar amounts of protein when 7 and 14 days old. The cellular content was evaluated by astroglial markers, such as the glial fibrillary acidic protein (GFAp; alpha-albumin) and the S-100 protein, and by markers for other cells expected to be in the cultures (14-3-2 protein, macrophage acidic protein (MAP), alkaline phosphatase, myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP]. Astroglial-like cells represented 60-70% of the cells present in the different cultures. Quantitation of GFAp (alpha-albumin) showed similar amounts to be present in cultures from cerebral cortex, hippocampus and striatum; however, on lower levels expressed in soluble proteins than in the corresponding brain regions of adult rats. Brainstem of adult rat contained large amounts of GFAp (alpha-albumin), while low levels were found in brainstem culture. Also, phagocytic cells (macrophages), endothelial-like cells, mesenchymal-like cells, ependymal-like cells and oligoblasts were found. Neither mature neurons, nor oligodendroglial cells were observed. It is concluded that although there might be some differences in the degree of maturation or in the cellular composition of the various cultures, they could serve as a good model system for studying the characteristics of astroglial cells from various brain regions.
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PMID:Cellular composition of primary cultures from cerebral cortex, striatum, hippocampus, brainstem and cerebellum. 673 69

Cultured murine oligodendrocytes elaborate extensive membrane sheets that, unlike multilamellar myelin in vivo, allow the study of interactions between myelin proteins and cytoskeletal elements. This article describes the events that occur due to the interaction of specific antibodies with their respective antigens, myelin/oligodendrocyte-specific protein (MOSP) and myelin/oligodendrocyte glycoprotein (MOG), which are expressed uniquely by oligodendrocytes. After antibody binding, surface anti-MOSP:MOSP complexes redistribute over those cytoplasmic microtubular veins that have 2',3'-cyclic nucleotide 3'-phosphohydrolase colocalized along them. In contrast, surface anti-MOG-MOG complexes redistribute over internal myelin basic protein domains. Long-term anti-MOSP IgM exposure results in an apparent increase in number as well as thickness of microtubular structures in oligodendrocyte membrane sheets, whereas long-term anti-MOG exposure causes depolymerization of microtubular veins in membrane sheets. These data suggest that antibody binding to these two surface proteins elicits signals that have opposite effects on the cytoskeleton in oligodendroglial membrane sheets. Thus, it is possible that signals transduced via antibody binding may contribute to the pathogenesis of diseases affecting CNS myelin.
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PMID:Antibodies to myelin/oligodendrocyte-specific protein and myelin/oligodendrocyte glycoprotein signal distinct changes in the organization of cultured oligodendroglial membrane sheets. 750 16

Production of CNS myelin by oligodendrocytes requires the regulated synthesis and assembly of cytoskeletal components. However, the molecular signals that mediate this process are not known. Here we use the shiverer mutant mouse, which is missing a large segment of the myelin basic protein (MBP) gene, to investigate the possible role in cytoskeletal assembly of an MBP gene product or of other myelin components whose expression may be linked to that of MBP. In axon-free cultures, we find that approximately half of shiverer oligodendrocytes have enlarged cell bodies, abnormal processes and fail to elaborate extensive membrane sheets. In those membrane sheets that are elaborated by shiverer oligodendrocytes, microtubular structures are abnormal in size and distribution. Additionally, 2',3'-cyclic nucleotide 3'-phosphohydrolase and microfilaments are not colocalized with microtubular structures as they would be in mature wild-type membrane sheets. These observations suggest that an MBP gene product has a direct or indirect role in regulating various aspects of cytoskeleton assembly in wild-type oligodendrocytes. In the absence of this signal, oligodendrocytes apparently do not normally assemble cytoskeleton; this may be one important basis for the abnormal morphology of intact shiverer CNS.
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PMID:Cytoskeleton in myelin-basic-protein-deficient shiverer oligodendrocytes. 754 83

We have used a combination of electrophysiological and biochemical approaches to investigate the effects and the mechanisms of action of tumor necrosis factor-alpha (TNF-alpha) on cultured oligodendrocytes (OLGs). Our studies have led to the following conclusions: (1) prolonged exposure of mature ovine OLGs to TNF-alpha leads to inhibition of process extension, membrane depolarization and a decrease in the amplitudes of both inwardly rectifying and outward K+ currents; (2) brief exposure of OLGs to TNF-alpha does not elicit membrane depolarization or consistent changes in cytosolic Ca2+ levels; (3) incubation of OLGs with TNF-alpha for 1 hr results in inhibition of phosphorylation of myelin basic protein and 2',3'-cyclic nucleotide phosphohydrolase. Ceramides, which have been shown to be effectors of TNF-alpha, are ineffective in inhibiting phosphorylation, whereas sphingomyelinase mimics TNF-alpha in this action. These observations suggest that other products of sphingomyelin hydrolysis may be the mediator(s) of TNF-alpha effect on protein phosphorylation. We have thus demonstrated that TNF-alpha can perturb the functions of OLGs via modulation of ion channels and of protein phosphorylation without necessarily inducing cell death. It is conceivable that modulation of ion channels and protein phosphorylation constitutes effective mechanisms for the participation of cytokines in signal transduction during myelination, demyelination and remyelination.
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PMID:Signal transduction pathways in oligodendrocytes: role of tumor necrosis factor-alpha. 757 87

We have previously established that 21-day-old postnatal rat oligodendrocytes, maintained in monolayer culture and subjected to 6 h of hypoxia, show reversible inhibition of synthesis of alpha-hydroxy fatty acid and myelin basic protein but a dramatic induction of a 22-kDa protein, suggesting that this is a good model to study the mechanism of CNS demyelination caused by hypoxic injury. We now report that hypoxia also dramatically inhibits the basal protein kinase C-mediated phosphorylation of myelin basic protein and myelin 2',3'-cyclic nucleotide phosphohydrolase by 80%, but that the inhibition of phosphorylation can be reversed by addition of a protein kinase C activator, phorbol 12-myristate 13-acetate. The mechanism of action appears to involve the uncoupling of signal transduction at a site before phospholipase C, because hypoxia did not affect protein kinase C activity or its translocation to the membrane fraction. The most potent activator of phospholipase C (as measured by inositol phosphate release) was carbachol (muscarinic M1 receptor agonist), followed by L-phenylephrine (alpha 1-adrenergic receptor agonist) in normal oligodendrocytes. Excitatory amino acids and histamine were ineffective. Hypoxia for 6 h completely inhibited both muscarinic and alpha 1-adrenergic receptor-mediated inositol monophosphate release but did not affect phospholipase D-coupled phosphatidylethanol production in response to carbachol. We therefore conclude from this and earlier work that early, reversible changes in oligodendrocyte metabolism result not simply from ATP depletion, but may specifically target GTP binding protein-mediated processes.
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PMID:Effects of hypoxia on oligodendrocyte signal transduction. 768 39

The goals of this study were to quantify myelin-associated changes in the brain following single doses of radiation and to determine their relationship to the dose limits that this tissue can tolerate. Mice developed a transient loss of balance 1 month after 60 Gy doses 250 kVp X-rays to the brain and 3-4 months after 30-45 Gy radiation, but not after lower doses. The symptoms were transient and lasted approximately 1 month. The ED50/300 for radiation-induced brain death, which occurred large between 200 and 240 days, was 32.4 Gy (29.1, 35.5 Gy, 95% confidence limit of mean). At the time that animals developed neurological symptoms, 3-4 months after irradiation with doses of 30-45 Gy, biochemical assays of myelin-associated proteins showed decreases in 2',3'-cyclic nucleotide phosphohydrolase (CNPase) and myelin basic protein (MBP) levels that were not seen with lower radiation doses. By 120-180 days, further dose-dependent decreases in both CNPase and MBP levels were found after 20-45 Gy irradiation that preceded and correlated with death. The correlation of the decrease in CNPase and MBP levels with the incidence of transient neurological malfunction and animal death, together with histological evidence, suggests that demyelination is responsible for these phenomena.
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PMID:Myelin-associated changes in mouse brain following irradiation. 769 73

Central nervous system myelin is elaborated by oligodendrocytes, which have been studied extensively in cell culture. Dissociated brain cultures allow in vitro analysis of events in myelinogenesis, including cell-cell interactions. Microglia, the primary phagocytic cell of the central nervous system, appear in developing fiber tracts prior to the onset of myelination in vivo. To gain insight into potential oligodendrocyte-microglial interactions during development, these cells were co-cultured and various parameters of myelin synthesis were measured. In co-culture, microglia stimulated the synthesis of sulfatide, a myelin-specific galactolipid, in oligodendrocytes, as well as the expression of the myelin-specific proteins myelin basic protein and proteolipid protein. Activity of the oligodendrocyte cytoplasm-specific enzyme 2',3'-cyclic nucleotide 3'-phosphohydrolase was not elevated, suggesting that the effects of microglia were not due to stimulation of oligodendrocyte proliferation. This was confirmed by the inability of microglia to induce significant DNA synthesis. Conditioned medium from cultured microglia provided a similar stimulatory activity, suggesting that the increase in myelin synthesis does not require contact between oligodendrocytes and microglia. These findings suggest a stimulatory role for microglia during myelinogenesis.
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PMID:Stimulation of in vitro myelin synthesis by microglia. 796 36

The potential for oligodendrocytes to proliferate in response to central nervous system injury was examined. We used intracerebral infection of Theiler's murine encephalomyelitis virus, a model for multiple sclerosis, which results in chronic demyelinating disease of SJL/J mice. Proliferating cells in spinal cord sections of adult mice were identified using simultaneous immunohistochemistry and in situ autoradiography ([3H]-thymidine incorporation). Seven different cell-specific markers were used to characterize proliferating cells as oligodendrocytes (myelin basic protein, proteolipid protein, galactocerebroside, CNPase), astrocytes (glial fibrillary acidic protein), microglia/macrophages (Griffonia simplicifolia isolectin B4) or T-lymphocytes (CD3). The average number of proliferating cells per area of spinal cord white matter was 11/mm2 in normal young adult mice compared to 61/mm2 in chronically infected mice. Most proliferating cells in normal spinal cord were not identified with these markers and were presumed to be progenitor glial cells. However, in spinal cord white matter of mice infected with Theiler's virus for approximately 4 months, 88% of proliferating cells were identified. Approximately one-third of all proliferating cells were in the oligodendrocyte lineage and expressed markers observed late in myelin differentiation. In demyelinated areas as compared to normal white matter, there was an 80- to 211-fold increase in the number of proliferating oligodendrocytes expressing myelin basic protein or proteolipid protein, respectively. The remainder of the proliferating cells in areas of demyelination were astrocytes, microglial cells and T-cells. These experiments support the hypothesis that factors within a demyelinating lesion promote the proliferation and differentiation of cells within the oligodendroglial lineage.
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PMID:The potential for oligodendrocyte proliferation during demyelinating disease. 838 Nov 62

Four human genomic DNA clones for 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) were isolated by screening a human genomic library with human CNP cDNA clones as probes. Restriction mapping and sequence analysis revealed that the human CNP gene is about 8.5 kb long and composed of four exons interrupted by three introns. There are two transcription start points and in human brain, two forms of CNP mRNA are produced from a single gene by alternative splicing, similar to mouse. A homology search of the 5'-flanking regions of exon 0 and exon 1 in the human CNP gene indicated the presence of oligodendroglia-specific elements and myelin basic protein transcription element (MBTE) motif, in addition to TATA-box-like sequences. Spot blot hybridization of flow-sorted human chromosomes with the 3'-noncoding region of the human CNP cDNA showed the localization of CNP to chromosome 17.
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PMID:Structure, expression and chromosomal localization of the gene encoding human 2',3'-cyclic-nucleotide 3'-phosphodiesterase. 839 17


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