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)

We attempted to define the critical time period during early postnatal life when GH and T4 are essential for myelination. We administered bGH and T4 to Snell dwarf mice during the first and second 20 days after birth. Positive results were obtained only when hormones were given during the first 20 days of postnatal life. We observed a distinct increase in brain weight, DNA content, CNPase activity and a remarkably increased level of spontaneous locomotion activity with a diurnal periodicity. Morphological observations of brain sections stained for myelin basic protein (MBP) correlated the biochemical findings. The later administration of hormones was ineffective. Our interpretation is that the administration of exogenous hormones led to increased myelinogenesis through their stimulatory effects on glial proliferation, as evidenced by the increase in cerebral DNA content.
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PMID:Cerebral myelinogenesis in the Snell dwarf mouse: stimulatory effects of GH and T4 restricted to the first 20 days of postnatal life. 241 44

Organotypic cultures of newborn rat brains were exposed to the neurotoxin kainic acid or the DNA synthesis inhibitor arabinoside C. The cultures were subsequently co-cultured and the myelination-related enzymatic activities, such as 2',3'-cyclic nucleotide phosphohydrolase and uridine diphosphate-galactose-ceramide galactosyl transferase, were determined under various culture conditions. The newly formed myelin basic protein in the cultured brain tissue was determined by the radioimmunoprecipitation method. The myelination-related enzymatic activities and the synthesis and accumulation of myelin basic protein in the co-cultured brain tissue were found compatible to the control cultures which were not exposed to either drug. The cultures which had been treated with either drug, but not subsequently co-cultured, were found to have decreased enzymatic activities and myelin basic protein synthesis. The experimental data suggest that myelinogenesis requires an interaction between functional neurons and oligodendroglial cells and further supports the hypothesis that the neuron exerts a regulatory effect on the glial myelination mechanism.
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PMID:Co-culture study of rat neuron-glial interaction: evidence of neuronal influence on myelination. 241 1

To determine whether GH has an independent action on cerebral development, we examined the central nervous system of the little mouse (lit), a promising model of isolated growth hormone deficiency. Our findings are (A); the weights of two parts of the lit brain were significantly less than those of the normal controls, 81.5% less for the cerebrum, and 81.6% for the cerebellum, (B): the total DNA content was reduced to approximately 80% in the cerebrum and 84% in the cerebellum compared to those of the normal controls, (C); the total RNA content was also reduced in the cerebrum and cerebellum, proportional to the reduction in DNA, (D); CNPase activity was reduced selectively in the cerebrum of the lit mouse (74.4% of the normal control), and (E); the lit mice exhibited a strikingly reduced level of activity with an indistinct diurnal periodicity. These results indicate that GH has independent actions on cerebral development, especially on glial cell proliferation as a precondition of myelin formation.
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PMID:Microcephalic cerebrum with hypomyelination in the growth hormone-deficient mouse (lit). 241 79

The time course of the appearance of myelin-specific markers was studied in the developing chick central nervous system (CNS). Chick CNS tissue was studied for the presence of both proteolipid and myelin basic protein by electroblotting and for 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) by enzyme assay. Four regions of chick spinal cord (cervical, brachial, thoracic and lumbar), brain stem, cerebellum, optic nerve and cortex were studied. In general, myelin basic protein appeared approximately 1 day earlier than proteolipid. In spinal cord and brain stem, myelin basic protein appeared at 13 days incubation. In cerebellum and optic nerve, it appeared at 17 days incubation and in cortex at hatching. CNPase activity increased in most CNS regions between 16 days incubation and hatching. These results suggest that myelination occurs earlier in the chick than in the rat and that it occurs over a shorter time period.
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PMID:Appearance of myelin proteins during development in the chick central nervous system. 241 27

The present paper establishes a 5'-polynucleotide kinase activity associated with the bovine and human brain enzyme 2':3'-cyclic nucleotide 3'-phosphodiesterase (EC 3.1.4.37) in addition to known extremely high hydrolysis rates against 2':3'-cyclic nucleotides. Modulation of the enzyme activity by the addition of polyadenylate (5') and polyuridylate (5'), histone F3, myelin basic protein (MBP), and other basic molecules suggest that RNA may be the natural substrate for both enzymes. These enzymes, isolated from brain and present in very high activities in oligodendrocytes and in isolated myelin, probably have complex functions.
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PMID:Inhibition of bovine and human brain 2':3'-cyclic nucleotide 3'-phosphodiesterase by heparin and polyribonucleotides and evidence for an associated 5'-polynucleotide kinase activity. 243 81

The myelin-associated glycoprotein (MAG) was quantitated in the CNS and PNS of quaking mice and the levels compared to the levels of myelin basic protein (MBP) and 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) activity. In the brainstems of 36-day-old quaking mice, MBP, MAG, and CNPase were reduced to 12, 16, and 29% of control levels, respectively. In the sciatic nerves of the 36-day-old quaking mice, MBP and CNPase were 38 and 75% of control levels, respectively, whereas the concentration of MAG was unchanged or slightly increased. Similar quantitative results were obtained for the sciatic nerves and spinal roots of 7-month-old quaking mice. Immunoblots showed that the principal MAG band from the brainstems, sciatic nerves, and spinal roots of the quaking mice had a higher than normal apparent Mr. In addition, there was a minor component reacting with anti-MAG antiserum in the brainstems of the quaking mice that had a slightly lower Mr than control MAG and was not detected in the normal mice. The results for the quaking mice are compared with those from similar studies on other mutants with dysmyelination of the CNS and PNS.
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PMID:Myelin-associated glycoprotein in the central and peripheral nervous system of quaking mice. 243 56

In order to study the biosynthesis of myelin-associated proteins in Schwann cells, we have induced proliferation of cultured Schwann cells from neonatal rat sciatic nerve by transformation with Simian Virus 40 (SV40). Homogeneous transformed Schwann cell lines were established by single cell cloning. The transformed phenotype of these Schwann cell lines was determined by both integration of SV40 viral DNA sequences into the cellular genome and active synthesis of the large T antigen of SV40. In addition, similar transformations with SV40 virus containing a temperature-sensitive mutation in the large T gene yielded Schwann cell lines with transformed phenotype which were temperature-sensitive. In this report, we demonstrate that these SV40-transformed Schwann cells actively synthesize myelin-specific sulfatide, myelin-associated glycoprotein (MAG) and the glial cell marker 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNPase). Despite the expression of MAG and CNPase, these Schwann cells did not synthesize PO the major protein of peripheral myelin. Since a substantial amount of normal size PO mRNA was present in these transformed Schwann cells, the lack of PO synthesis was apparently not the result of a deficiency of transcription. These results are consistent with the possibility that the regulation of PO synthesis differs from that of MAG and CNPase synthesis and that PO synthesis may be controlled at the post-transcriptional level.
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PMID:Biosynthesis of myelin-associated proteins in simian virus 40 (SV40)-transformed rat Schwann cell lines. 244

Monoclonal antibodies against human and bovine 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) were generated by fusing FOX-NY myeloma cells with spleen cells from RBF/Dn mice previously immunized with the purified brain antigens. The enzyme isolated from bovine brain was quite basic, with an isoelectric point of 9.71 and both the bovine and human enzymes consisted of a closely spaced doublet at approximately 44 and 46 kDa on SDS-PAGE. Six monoclonals were were identified as strongly recognizing the enzyme on both ELISA plates and on immunoblots of whole brain protein. Four monoclonals very weakly cross-reacted with guinea pig myelin basic protein. In contrast with two previous reports, some of our monoclonal antibodies did immunostain 2 or 3 protein bands in peripheral nerve, two bands closely corresponding to those immunostained in central nervous system (CNS) myelin, the Wolfgram protein fraction and in acetone powders of whole brain. Each of the 6 monoclonals reacting strongly on immunoblots recognized the enzyme in from 2 to 5 of the species examined (human, bovine, rat, mouse and rabbit). In addition, all 6 monoclonals that immunostained the enzyme in whole brain, myelin and Wolfgram protein immunoblots recognized both CNP1 (44 kDa) and CNP2 (46 kDa). The two closely spaced protein bands observed on SDS-PAGE and previously stained on immunoblots of CNS CNPase using polyvalent rabbit anti-bovine CNPase antisera, and now different monoclonal antibodies, appear to be immunologically related and to contain highly conserved sequences.
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PMID:Monoclonal antibody production to human and bovine 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNPase): high-specificity recognition in whole brain acetone powders and conservation of sequence between CNP1 and CNP2. 244 13

We report the development of a simple and reliable method for the study of demyelination in vitro based on the measurement of 2':3'-cyclic nucleotide 3'-phosphodiesterase in isolated myelin. Using only small quantities of myelin (equivalent to 100 micrograms of myelin protein) the system was tested under conditions that are believed to approximate those found at the site of an inflammatory demyelinating lesion. Treatment with a combination of trypsin, phospholipase A2, and lysophosphatidylcholine was used to evaluate the method. This microsystem has the potential not only for testing the myelinotoxicity of soluble factors but also for investigating the involvement of inflammatory cells in the demyelinating process. Myelin degradation by elicited peritoneal macrophages could be demonstrated at relatively high densities of these cells. Nylon wool purified lymph node T cells from myelin basic protein-primed SJL/J mice, after selective expansion with antigen and interleukin 2, failed to induce any significant myelin breakdown unless a limited number of syngeneic activated macrophages were also present. T cells from mice that had been inoculated with keyhole limpet haemocyanin failed to show any effect. The advantages of this technique over other in vitro systems are that it enables the study of demyelination using syngeneic sources of myelin and defined cell populations.
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PMID:An in vitro micromethod for the quantitative assessment of central demyelination. 245 36

We have analyzed the effects of genetic and epigenetic factors on the steady-state levels of myelin basic protein mRNA and polypeptides during development of mouse oligodendrocytes in culture. Oligodendrocytes were characterized by immunofluorescent staining with antibodies for the following markers: galactocerebroside, myelin basic protein, proteolipid protein, myelin-associated glycoprotein and 2',3'-cyclic nucleotide phosphohydrolase. Oligodendrocytes expressing one or more of these markers first appeared at 3 days in culture and increased to a maximum of 1.5 X 10(5) per brain around 6 days, after which the number remained constant up to 31 days. In medium containing fetal calf serum, accumulation of myelin basic protein polypeptides was delayed relative to in vivo in cultures derived from C57BL/6J, BALB/cJ and DBA/2J inbred mice, but not in cultures derived from C3H/HeJ and AKR/J inbred mice. In medium containing serum from other species or in serum substitute, the temporal expression of myelin basic protein polypeptides in cultures from all the inbred strains was contemporaneous with that in brain. Northern hybridization analysis indicated that the steady-state level of myelin basic protein-specific mRNA in all cultures was regulated similarly to in vivo suggesting that the delayed expression of myelin basic protein polypeptides in some cultures was due to translational and/or post-translational regulation. Analysis of myelin basic protein expression in cultures from informative hybrid and recombinant inbred strains indicated that translational or post-translational expression of myelin basic protein requires trans-acting factors, the inducibility of which is controlled by multiple genetic determinants which segregate independently and are expressed additively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of myelin basic protein mRNA and polypeptides in mouse oligodendrocytes in culture: differential regulation by genetic and epigenetic factors. 245 46


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