Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.37 (CNPase)
 539 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously reported that human amniotic epithelial (HAE) cells expressed neuronal and glial cell markers using immunostaining and western blotting. To study the expression system of these cell markers in HAE cells, we investigated the expression of mRNA for oligodendrocyte markers in HAE cells by reverse-transcriptase-polymerase chain reaction (RT-PCR) and northern blotting. Neural cell-specific expression system was used to examine the transcriptional activity of myelin basic protein (MBP). Oligodendrocyte markers were expressed such as CNPase, MBP and proteolipid protein (PLP and DM-20). PLP gene transcripts in the cells were in a lower level than DM-20, compared with those of human brain. Neural cell-type-specific expression system disclosed HAE cells were about 20% positive for beta-Gal using AdexMBP-NL-LacZ. This strongly indicates that HAE cells have MBP-specific gene expressing cells.
 ...
PMID:Gene expression of oligodendrocyte markers in human amniotic epithelial cells using neural cell-type-specific expression system. 1040 22

The basic helix-loop-helix transcription factor c-Myc is a potent trigger of programmed cell death when overexpressed during late oligodendrocyte development in transgenic mice. Here we provide evidence that c-Myc can act synergistically with the Pit, Oct, Unc homeodomain transcription factor Oct-6 to produce myelin disease pathogenesis in transgenic mice. More than 70% of c-myc/Oct-6 bitransgenic mice, obtained from crosses between phenotypically normal heterozygous mice of various My (c-Myc) and Oc (Oct-6) transgenic strains that express c-myc and oct-6 transgenes under transcriptional control of the myelin basic protein gene, developed severe neurological disturbances characterized by action tremors, recurrent seizures, and premature death. Affected bitransgenic mice exhibited multiple hypomyelinated lesions in the white matter that did not stain with myelin-specific antibodies against myelin basic protein, proteolipid protein, CNPase, and myelin-associated glycoprotein. The mice also exhibited a larger number of terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling positive cells in the white matter as well as ultrastructural evidence of glial cell death and astrogliosis. These observations indicate that the myelin lesions observed in the c-myc/oct-6 bitransgenic mice result from the untimely programmed cell death of oligodendroglia and that the c-myc and oct-6 transgenes act synergistically in producing the lesions.
 ...
PMID:Oligodendrocyte programmed cell death and central myelination deficiency induced in transgenic mice by synergism between c-Myc and Oct-6. 1051 74

Oligodendrocytes have a high rate of synthetic activity and produce vast amounts of myelin. The membrane production requires specific sorting and transport processes and structural support. In culture, oligodendrocytes extend flat membranous sheets containing an extensive cytoskeletal network of microtubules (MTs) and microfilaments (MFs). The microtubules participate in the elaboration and stabilization of the myelin-containing cellular processes and have an impact not only on the complex oligodendroglia architecture but also influence their functions. They participate in intracellular sorting processes and the translocation of myelin basic protein (MBP) mRNAs to the forming myelin sheath. The two major groups of neuronal microtubule-associated proteins (MAPs), MAP2 and tau are expressed in oligodendrocytes and might be involved in the regulation of MT stability and organization. Myelin-specific proteins, such as MBP and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP), interact with the cytoskeleton. Glial changes occur in a variety of neurodegenerative diseases, and glial fibrillary tangles and glial cytoplasmic inclusions (GCls), containing abnormal microtubular structures which stain positively for stress proteins and microtubule-associated proteins, are found in oligodendrocytes of the affected brains. The role of MTs and their associated proteins in oligodendrocytes during normal development and pathological situations is specifically emphasized in this review.
 ...
PMID:The oligodendroglia cytoskeleton in health and disease. 1065 80

In previous work we found that mezerein, a C kinase activator, as well as basic fibroblast growth factor (FGF-2) induce demyelination and partial oligodendrocyte dedifferentiation in highly differentiated aggregating brain cell cultures. Here we show that following protein kinase C activator-induced demyelination, effective remyelination occurs. We found that mezerein or FGF-2 caused a transient increase in DNA synthesis following a pronounced decrease of the myelin markers myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphohydrolase. Both oligodendrocytes and astrocytes were involved in this mitogenic response. Within 17 days after demyelination, myelin was restored to the level of the untreated controls. Transient mitotic activity was indispensable for remyelination. The present results suggest that myelinating oligodendrocytes retain the capacity to reenter the cell cycle, and that this plasticity is important for the regeneration of the oligodendrocyte lineage and remyelination. Although it cannot be excluded that a quiescent population of oligodendrocyte precursor cells was present in the aggregates and able to proliferate, differentiate and remyelinate, we could not find evidence supporting this view.
 ...
PMID:Remyelination in vitro following protein kinase C activator-induced demyelination. 1151 22

To link the presence of intrathecal virus-specific oligoclonal immunoglobulin G (IgG) in multiple sclerosis patients to a demyelinating activity, aggregating rat brain cell cultures were treated with antibodies directed against two viruses, namely, rubella (RV) and hepatitis B (HB). Anti-RV antibodies in the presence of complement decreased myelin basic protein concentrations in a dose-dependent manner, whereas anti-HB antibodies had no effect. A similar but less pronounced effect was observed on the enzymatic activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase, which is enriched in noncompact membranes of oligodendrocytes. These effects were comparable to those in cultures treated with antibodies directed against myelin oligodendrocyte glycoprotein (MOG), previously found to be myelinotoxic both in vitro and in vivo. Sequence homologies were found between structural glycoprotein E(2) of RV and MOG, suggesting that demyelination was due to molecular mimicry. To support the hypothesis that demyelination was caused by anti-RV IgG that recognized an MOG epitope, we found that anti-RV antibodies depleted MOG in a dose-dependent manner. Further evidence came from the demonstration that anti-RV and anti-MOG IgG colocalized on oligodendrocyte processes and that both revealed by Western blot a 28 kDa protein in CNS myelin, a molecular weight corresponding to MOG. These findings suggest that a virus such as RV exhibiting molecular mimicry with MOG can trigger an autoimmune demyelination.
 ...
PMID:Antibodies directed against rubella virus induce demyelination in aggregating rat brain cell cultures. 1153 29

Spinal cord white matter is susceptible to AMPA/kainate (KA)-type glutamate receptor-mediated excitotoxicity. To understand this vulnerability, it is important to characterize the distribution of AMPA/KA receptor subunits in this tissue. Using immunohistochemistry and laser confocal microscopy, we studied the expression sites of AMPA/KA receptor subunits in mouse spinal cord. The white matter showed consistent immunoreactivity for AMPA receptor subunit GluR2/3 and KA receptor subunits GluR6/7 and KA2. In contrast, antibodies against GluR1, GluR2, GluR4 (AMPA), and GluR5 (KA) subunits showed only weak and occasional labeling of white matter. However, gray matter neurons did express GluR1 and GluR2, as well as GluR2/3. The white matter astrocytes were GluR2/3 and GluR6/7 immunopositive, while the gray matter astrocytes displayed primarily GluR6/7. Both exclusively and abundantly, KA2 labeled oligodendrocytes and myelin, identified by CNPase expression. Interestingly, myelin basic protein, another myelin marker, showed less correlation with KA2 expression, placing KA2 at specific CNPase-containing subdomains. Focal points of dense KA2 labeling showed colocalization with limited, but distinct, axonal regions. These regions were identified as nodes of Ranvier by coexpressing the nodal marker, ankyrin G. Overall, axonal tracts showed little, if any, AMPA/KA receptor expression. The proximity of oligodendrocytic KA2 to the axonal node and the paucity of axonal AMPA/kainate receptor expression suggest that excitotoxic axonal damage may be secondary and, possibly, mediated by oligodendrocytes. Our data demonstrate differential expression of glutamate AMPA and KA receptor subunits in mouse spinal cord white matter and point to astrocytes and oligodendrocytes as potential targets for pharmacological intervention in white matter glutamate excitotoxicity.
 ...
PMID:AMPA/kainate receptors in mouse spinal cord cell-specific display of receptor subunits by oligodendrocytes and astrocytes and at the nodes of Ranvier. 1259 33

Vacuolar myelopathy (VM) is a frequent central nervous system complication of human immunodeficiency virus type 1 (HIV-1) infection. We report here that transgenic (Tg) mice expressing even low levels of Nef in oligodendrocytes under the regulation of the myelin basic protein (MBP) promoter (MBP/HIV(Nef)) developed VM similar to the human disease in its appearance and topography. The spinal cords of these Tg mice showed lower levels of the myelin proteins MAG and CNPase and of the 21-kDa isoform of MBP prior to the development of vacuoles. In addition, Tg oligodendrocytes in primary in vitro cultures appeared morphologically more mature but, paradoxically, exhibited a less mature phenotype based on O4, O1, CNPase, and MBP staining. In particular, mature CNPase(+) MBP(+) Tg oligodendrocytes were less numerous than non-Tg oligodendrocytes. Therefore, Nef appears to affect the proper differentiation of oligodendrocytes. These data suggest that even low levels of Nef expression in human oligodendrocytes may be responsible for the development of VM in HIV-1-infected individuals.
 ...
PMID:Oligodendrocyte-specific expression of human immunodeficiency virus type 1 Nef in transgenic mice leads to vacuolar myelopathy and alters oligodendrocyte phenotype in vitro. 1455 59

Iron deficiency in early life is associated with hypomyelination; however, the role which iron plays in myelinogenesis is not clearly established. In this study, we examined the effect of preweaning [postnatal days (PND) 4-14 and PND 4-21] and postweaning (PND 21-63) iron deficiency on hindbrain 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) activity (marker of oligodendrocyte metabolic activity) and myelin basic protein (MBP) concentrations. Both CNPase activity and concentrations in the cerebrum and hindbrain were significantly lower in pre- and postweaning iron-deficient rats. Similarly, MBP concentrations were also reduced (25-35%) in all three groups of iron-deficient animals. Iron-deficient animals also had significant alterations in the fatty acid composition of individual phospholipids within the hindbrain as well as changes in cytochrome oxidase activities. These studies show that postnatal iron deficiency, for as little as 10 days, can significantly alter the production of myelin and oligodendrocyte functioning. Importantly, postweaning iron deficiency was still associated with a decrease in CNPase activity and MBP concentrations despite occurring well past a likely key sensitive period of peak myelinogenesis at PND 8-12. This suggests that iron deficiency in later life, as well as during early postnatal growth, can effect the production and maintenance of myelin.
 ...
PMID:Pre- and postweaning iron deficiency alters myelination in Sprague-Dawley rats. 1461 57

Bone marrow, or cells selected from bone marrow, were reported recently to give rise to cells with a neural phenotype after in vitro treatment with neural-inducing factors or after delivery into the brain. However, we showed previously that untreated bone marrow cells express products of the neural myelin basic protein gene, and we demonstrate here that a subset of ex vivo bone marrow cells expresses the neurogenic transcription factor Pax-6 as well as neuronal genes encoding neurofilament H, NeuN (neuronal nuclear protein), HuC/HuD (Hu-antigen C/Hu-antigen D), and GAD65 (glutamic acid decarboxylase 65), as well as the oligodendroglial gene encoding CNPase (2',3' cyclic nucleotide 3'-phosphohydrolase). In contrast, astroglial glial fibrillary acidic protein (GFAP) was not detected. These cells also were CD34+, a marker of hematopoietic stem cells. Cultures of these highly proliferative CD34+ cells, derived from adult mouse bone marrow, uniformly displayed a phenotype comparable with that of hematopoietic progenitor cells (CD45+, CD34+, Sca-1+, AA4.1+, cKit+, GATA-2+, and LMO-2+). The neuronal and oligodendroglial genes expressed in ex vivo bone marrow also were expressed in all cultured CD34+ cells, and GFAP was not observed. After CD34+ cell transplantation into adult brain, neuronal or oligodendroglial markers segregated into distinct nonoverlapping cell populations, whereas astroglial GFAP appeared, in the absence of other neural markers, in a separate set of implanted cells. Thus, neuronal and oligodendroglial gene products are present in a subset of bone marrow cells, and the expression of these genes can be regulated in brain. The fact that these CD34+ cells also express transcription factors (Rex-1 and Oct-4) that are found in early development elicits the hypothesis that they may be pluripotent embryonic-like stem cells.
 ...
PMID:Hematopoietic progenitors express neural genes. 1463 11

White matter damage (WMD) is an important cause of disability including cerebral palsy in preterm, low birth-weight infants. Maternal infection is now recognized as one of the risk factors for WMD. Previously we reported that intrauterine inoculation of Escherichia coli to pregnant rats resulted in WMD in offspring and interleukin-10 (IL-10) was protective against this damage. The objective of this study was to elucidate the mechanism involved in the protective effect of IL-10 against neonatal WMD. We found that E. coli treatment in dams resulted in significant apoptosis in periventricular white matter of rat pups on postnatal day 0 (P0). On P8, a remarkable increase in ED-1 immunostaining (indicating either microglial activation or macrophage infiltration) was detected in brains of pups in the E. coli-treated group. Astrogliosis was also noticed in brain white matter of pups in the E. coli-treated group. In addition to the strong activation of microglia and astrocytes, oligodendrocytes (OLs) were significantly reduced in periventricular areas in the brains of pups from the E. coli-treated group. Later, on P15, hypomyelination was also noticed in rat brains from the E. coli-treated group, using myelin basic protein (MBP) immunostaining. Treatment with IL-10 after E. coli inoculation significantly reduced TUNEL staining and caspase-3 activation, and partially restored the impaired immunostaining markers for immature and mature OLs, such as CNPase, O4, adenomatous polyposis coli (APC) and MBP. These results indicate that the protective effect of IL-10 against brain WMD is linked with suppression of microglial activation/macrophage infiltration, as shown by significantly reduced ED-1+ cells in the white matter.
 ...
PMID:Suppression of glial activation is involved in the protection of IL-10 on maternal E. coli induced neonatal white matter injury. 1587 85


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