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)

Schwann cells are responsible for the maintenance of the peripheral myelin sheath and neurotoxic insult directed against these cells can result in demyelination with a concomitant loss of neural function. We have utilized several in vitro techniques to investigate the effects of neurotoxins on the complex interactions between SC and axons. SC may be isolated from fresh neonatal sciatic nerves and used to examine the effect of neurotoxins on the axonal membrane induction of SC proliferation and specific myelin protein mRNA expression. We have recently devised a method to obtain SC from frozen sciatic nerves. This method allows pooling of neonatal nerves to generate enough cells for subsequent study. We have also transfected primary Schwann cells with a plasmid containing the large T antigen to obtain a SC line suitable for neurotoxicology studies. The functional status of cultured SC may also be studied via expression of SC specific antigens such as glial fibrillary acidic protein, CNPase, S100, laminin, P0 and myelin basic protein. We also propose culturing SC with dorsal root ganglion neurons to investigate the effect of neurotoxins on all stages of SC maturation, from proliferation to the in vitro synthesis of a compact myelin sheath. These strategies will allow us to investigate the cellular mechanisms of neurotoxicity in the PNS.
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PMID:In vitro use of Schwann cells to elucidate neurotoxic injury. 174 36

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

The relative levels of the central nervous system myelin marker enzyme 2':3'-cyclic nucleotide 3'-phosphodiesterase (EC 3.1.4.37, CNPase) were determined in neuroblastoma, astrocyte, oligodendrocyte and Schwann cell cultures and in freshly isolated human lymphocytes and platelets. The highest specific activities were associated with the cells that elaborate myelin membrane in the central and peripheral nervous system, oligodendrocytes and Schwann cells, respectively. Antiserum to bovine CNPase recognized both CNP1 and CNP2 in CNS myelin and human oligodendroglioma. In addition, a 53,000 dalton protein was evident on autoradiographs of immunoblotted PNS myelin and human oligodendroglioma proteins. Cultured rat oligodendrocyte, C6 and mouse NA neuroblastoma CNPase appear to share common determinants with the corresponding normal rat CNS enzyme.
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PMID:Differential expression of 2':3'-cyclic nucleotide 3'-phosphodiesterase in cultured central, peripheral, and extraneural cells. 299 54

Shiverer mouse is characterized by poor lamella formation and absence of major dense line in the CNS myelin. PNS of the Shiverer was normal with regard to myelin lamellar formation, immunohistochemical staining of the Schwann cells by S-100 protein, and the activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase. Analysis of the purified myelin by SDS-polyacrylamide gel electrophoresis revealed that P1 and Pr, which are common to BP in CNS, and PM protein were missing, while P0 and P2 proteins were of the same level as the control.
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PMID:Neurochemical and morphological studies on the myelin of peripheral nervous system from Shiverer mutant mice: absence of basic proteins common to central nervous system. 616 75

Peripheral nerves of the shiverer mouse, which are characterized by the absence of major dense lines and myelin basic proteins in CNS myelin, were analyzed. From subcellular fractionation of sciatic nerves, it was found from the SDS-polyacrylamide gel electrophoresis that the Pl and Pr proteins equivalent to myelin basic protein of CNS and PM protein were missing in the shiverer in both P2A and P3A fractions in which PNS myelin is recovered. No extra bands were observed in any other fractions of the shiverer in place of the absence of the proteins. The activities of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) of P2A and P3A fractions were high, but that of the P3X fraction which floated over 0.32 M sucrose was the highest among the fractions examined in both the shiverer and the control. Developmental analysis of the protein profiles revealed that PO, Pl, Pr and PM proteins increased rapidly from the sixth day postnatally up to the twentieth day after birth in the control. No differences were observed between the shiverer and the control as for PO protein, but Pl, Pr and PM proteins were absent in the shiverer throughout the development. The CNPase activity of total homogenate of sciatic nerve fibers at birth in the control showed high activity comparable to that of the adult value, but there was no significant difference in activity between the control and the shiverer at any stage of development. Immunohistochemical reaction using peroxidase anti-peroxidase method showed that the myelin from the shiverer did not react with the MBP antiserum, while that of the control reacted positively. On the contrary, the myelin from both shiverer and the control reacted positively against P2 antibody.
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PMID:Peripheral nervous system of shiverer mutant mice: developmental change of myelin components and immunohistochemical demonstration of the absence of MBP and presence of P2 protein. 618 16

Two fractions were isolated by continuous density gradient centrifugation from total particulate matter of rabbit sciatic nerves: a minor fraction, B, consisting of small-sized membrane fragments and a major fraction, C, of characteristic multilayered myelin figures, with maxima at 0.33 and 0.58 M-sucrose, respectively. In comparison with C, fraction B was enriched in CNPase and alkaline phosphatase activities and the P0, 23K and Z proteins, but was virtually devoid of basic protein. The glycoprotein composition of all fractions was examined with four fluorescein isothiocyanate-labelled lectins (WGA, Con A, RCA-60, U.E.). These revealed the presence of six glycoproteins in all fractions with similar lectin binding capacities and molecular weights ranging from 35,500 to 16,000, of which P0 was the predominant component. Material found on the heavy side of fraction C was characterized by the presence of a multitude of glycoproteins which bound variable proportions of the four different lectins, suggesting substantial variations in their carbohydrate moieties. Their absence from the central portion of fraction C points to a location other than that of compact PNS myelin.
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PMID:The glycoprotein composition of peripheral nervous system myelin subfractions. 679 Jun 71

Mounting evidence suggests that autoantibodies contribute to the pathogenesis of demyelination in the PNS and CNS. Rapid reversal of electrophysiological blockade after plasmapheresis or intravenous immunoglobulin treatment for acute or chronic inflammatory demyelinating polyneuropathy is more likely to result from removal or neutralization of an antibody that impairs saltatory conduction than from remyelination. Although up to 30% of patients with acute or chronic inflammatory demyelinating polyneuropathy harbour autoantibodies, specific antigens have been identified in no more than 13% of cases. To date, autoantigens identified at the node of Ranvier include neurofascin 186, gliomedin and possibly moesin in the nodal domain, and contactin-1, Caspr1 and neurofascin 155 in the paranodal domain. In some patients with multiple sclerosis, paranodal CNPase and juxtaparanodal contactin-2 trigger a humoral response. This Review explores the molecular anatomy of the node of Ranvier, focusing on proteins with extracellular domains that could serve as antigens. The clinical implications of node-specific antibody responses are addressed, and the best approaches to identify antibodies that target nodal proteins are highlighted. Also discussed are the roles of these antibodies as either secondary, disease-exacerbating responses, or as a primary effector mechanism that defines demyelination or axonal degeneration at the node, identifies disease subtypes or determines response to treatments.
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PMID:Autoimmune antigenic targets at the node of Ranvier in demyelinating disorders. 2562 93