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)

In order to assess the sensitivity of several cell specific enzyme markers (tyrosine hydroxylase (TH), glutamic acid decarboxylase, choline acetyltransferase, glutamine synthetase (GS), neuron specific and non-neuronal enolase and 2',3'-cyclic nucleotide phosphohydrolase (CNP] as indices of neurotoxicity, changes in their activities were monitored after rats were treated with two doses of the neurotoxic agent, methylmercury chloride (MMC). Comparisons were also made of any histopathological changes occurring in the tissues examined. At the low dose rate (3.36 mg Hg/kg, po, for 14 days), the rats exhibited less body weight gain compared to untreated animals. No change in either the neuronal or noneuronal enzyme markers was observed in brain but a significant increase in the myelin marker, CNP, and total enolase activity was seen in the optic nerve. Morphological evaluation by light microscopy indicated no discernible neuronal lesions in MMC-exposed animals. At the higher MMC dose (7.05 mg Hg/kg, po, for 7 days), there was about a 20% loss in the body weight of treated animals and partial hind limb paralysis was observed. Of all the neuronal marker enzymes examined, only TH was found to be decreased in the striatum. The proliferating astroglial marker, GS, was elevated only in the cerebellum. CNP was found to be decreased in both the optic and sciatic nerve. As in the lower dose group no pathological changes were observed at the light microscopic level in the brain of MMC-treated rats. These data suggest that of the cell specific marker enzymes studied, GS in the cerebellum and TH in the striatum may be useful biochemical markers for the neurotoxic action of MMC.
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PMID:Cell specific enzyme markers as indicators of neurotoxicity: effects of acute exposure to methylmercury. 257 Mar 89

The in vitro effect of methylmercury (MM) on the enzymatic activities of brain cell specific marker enzymes, choline acetyltransferase (CAT), glutamic acid decarboxylase (GAD), 2',3'-cyclic nucleotide phosphohydrolase (CNP), glutamine synthetase (GS) and enolase was examined. The results demonstrate that at 100 microM MM, GS activity was not affected whereas a small decrease in the activity of both GAD (20%) and enolase (10%) was observed. CNP and CAT activity appeared to be more sensitive toward MM with 100 microM MM producing inhibition of 50% and 30%, respectively. The addition of sulfhydryl protecting reagents such as DTT or sodium thioglycolate can restore the enzyme activities to normal control levels despite prior exposure of the enzymes to MM.
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PMID:Studies of the in vitro effect of methylmercury chloride on rat brain neurotransmitter enzymes. 288 7

Seven cell specific marker enzymes in brain and optic nerve and morphological evaluation by light microscopy were used to characterize the neurotoxicity associated with exposure of rats to hexachlorophene (HCP; 40 mg/kg/day, po, for 9 days). In vitro exposure to HCP at concentrations up to 100 microM had no direct inhibitory effect on the marker enzymes, validating their use in evaluating brain function in vivo. Rats exhibited a reduction in body weight gain, weakness, and ataxia of the hind limbs by the ninth day of HCP exposure. At 24 hr following the last day of exposure to HCP, the activities of the three neuron specific enzymes, glutamic acid decarboxylase, tyrosine hydroxylase, and choline acetyltransferase, in rat brain were unchanged from those of the vehicle-treated control group. Of the two astroglial enzyme markers measured, a small but significant increase was observed in the activity of nonneuronal enolase in the cerebellum and glutamine synthetase in the hippocampus of HCP-treated rats. The optic nerve appeared to be the most sensitive tissue in that the activity of both the astroglial marker, nonneuronal enolase, and the myelin marker, 2',3'-cyclic nucleotide phosphohydrolase, was significantly decreased following HCP exposure. This decrease in enzyme activity is consistent with the histological observations demonstrating extensive vacuolization and edema in the optic nerve after exposure to HCP.
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PMID:Effect of short-term exposure to hexachlorophene on rat brain cell specific marker enzymes. 290 23

In order to define the locus of acrylamide neurotoxicity, the effects of chronic intoxication (total dose 500 mg/kg) on cholinergic synthesis and transport, the Schwann cell-myelin complex, lysosomal activity, and several metabolic pathways were determined in rat sciatic nerve, spinal cord, and brain. No changes were found in hematological measures or in the levels of clinically important blood enzymes, indicating no major damage to other organs. The activities of choline acetyltransferase (ChAT), 2',3'-cyclic nucleotide phosphohydrolase, beta-glucuronidase, and lactate dehydrogenase were unaffected in acrylamide paralyzed animals, but creatine kinase (CK) decreased in sciatic nerve, muscle, and brain, particularly in animals dying of the intoxication. CK blood and the CK isoenzyme patterns in blood were unchanged. The synthesis of protein in brain and spinal cord (measured in vivo) were decreased in rats exposed to high-dose acrylamide. However, in brain and cord, CK decreased only after animals became systemically ill and suffered weight loss, with the lowest activities in those animals sick enough to die. The degree of stress to which the animals had been subjected was indicated by enlargement of the adrenal glands and decreased sulfolipid synthesis in the adrenals. Rats exposed to 25 mg/kg/day acrylamide to a total dose of 250 mg/kg developed leg weakness but not paralysis or weight loss and had a 25% decrease in CK only in the distal sciatic nerve. Because of the apparently stress-related or agonal loss of CK, no specific effect of acrylamide on the enzyme could be definitely demonstrated. Neither could the changes in protein synthesis be attributed solely to a direct effect of the toxin. These results illustrate the difficulties encountered in interpreting intoxication studies that produce systemic illness and support the suggestion that CK activity may be a useful marker of the severity and duration of the agonal state in studies of postmortem human brain.
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PMID:The influence of systemic factors on acrylamide-induced changes in brain, nerve, and other tissues. 608 44

A biochemical study of a case affected by Creutzfeldt-Jakob disease is reported. Changes were found in soluble and insoluble proteins, glycoproteins and mucopolysaccharides and in total lipids, glycolipids, phospholipids and gangliosides. Also CNPase, choline acetyltransferase, 5'-nucleotidase and several glycosidases have an altered activity. All these data give a complete neurochemical pattern of the changes underlying the morphological and functional alterations in this disease.
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PMID:Neurochemical changes in Creutzfeldt-Jakob disease. 615 3

Heterosis (hybrid vigor) for brain myelin content has been examined in detail in (C57BL/6J x DBA/2J)F1 hybrid mice at 17 days of age. The amount of myelin isolated from the F1 hybrid brain is greater than that isolated from either parental strain. In addition, the total protein content in the myelin of the three genotypes showed the following trend: F1 greater than DBA greater than C57. However, no discernible differences in myelin protein compositions could be detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Analysis of the whole brain for several myelin-associated constituents such as GM1 ganglioside, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase), 5'-nucleotidase, and carbonic anhydrase indicated that heterosis exists for these components. No heterosis was found for such nonmyelin constituents as gangliosides GD1a, GT, GQ, RNA, DNA, and choline acetyltransferase. A developmental study of the whole brain CNPase indicated that the heterotic effect was greatest during the most active period of myelination (17-30 days). We conclude that the heterotic effect is specific for myelin content and is probably the result of an accelerated myelin synthesis. The heterotic effect should have great potential as a new model for studying aspects of myelinogenesis.
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PMID:Biochemical study of heterosis for brain myelin content in mice. 618 36

Immunohistochemical reactions were conducted, using the antibodies against GFA and S-100 proteins on sections of cerebellum from the homozygous (jj) and the heterozygous (Jj) Gunn rats. Hypertrophy of the fibrous astrocytes was observed but hyperplasia of the glial cells was not. Although the molecular layer was very thin, the Bergmann fibre appeared normal. Among the free amino acids in the cerebellum from the jj rat, glutamate concentration decreased to two-thirds of the control level. The protein profile of the cerebellum from the jj rat obtained by SDS-polyacrylamide gel electrophoresis revealed that the amount of P400 protein that is characteristic of Purkinje cells decreased considerably and there were also some changes of the other unidentified proteins. By two-dimensional electrophoresis, it was observed that in the supernatant from the jj rat cerebellum one protein spot diminished and in the particulate fraction from the jj rat one spot was enormously increased. The activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) in the cerebellum from the jj rat did not differ significantly from that of the control; however, activities of choline acetyltransferase and acetylcholinesterase of the jj rat were about twice as high as those of the control. 2-Deoxyglucose incorporation was maximum in the granular layer from both the jj and the Jj rat cerebella. However, the incorporation in the jj cerebellum was not higher than in the Jj control and even lower in some parts of the jj cerebellum than in the control Jj cerebellum.
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PMID:Cerebellar hypoplasia in the Gunn rat with hereditary hyperbilirubinemia: immunohistochemical and neurochemical studies. 625 97

The involvement of voltage-gated calcium channels in the survival of immature CNS neurons was studied in aggregating brain cell cultures by examining cell type-specific effects of various channel blockers. Nifedipine (10 microM), a specific blocker of L-type calcium channels, caused a pronounced and irreversible decrease of glutamic acid decarboxylase activity, whereas the activity of choline acetyltransferase was significantly less affected. Flunarizine (1-10 microM, a relatively unspecific ion channel blocker) elicited similar effects, that were attenuated by NMDA. The glia-specific marker enzymes, glutamine synthetase and 2',3'-cyclic nucleotide 3'-phosphohydrolase, were affected only after treatment with high concentrations of nifedipine (50 microM) or NiCl2 (100 microM, shown to block T-type calcium channels). Nifedipine (50 microM), NiCl2 (100 microM), and flunarizine (5 microM) also caused a significant increase in the soluble nucleosome concentration, indicating increased apoptotic cell death. This effect was prevented by cycloheximide (1 microM). Furthermore, the combined treatment with calcicludine (10 nM, blocking L-type calcium channels) and funnel-web spider toxin-3.3 (100 nM, blocking T-type channels) also caused a significant increase in free nucleosomes as well as a decrease in glutamic acid decarboxylase activity. In contrast, cell viability was not affected by peptide blockers specific for N-, P-, and/or Q-type calcium channels. Highly differentiated cultures showed diminished susceptibility to nifedipine and flunarizine. The present data suggest that the survival of immature neurons, and particularly that of immature GABAergic neurons, requires the sustained entry of Ca2+ through voltage-gated calcium channels.
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PMID:High sensitivity of immature GABAergic neurons to blockers of voltage-gated calcium channels. 1036 97

To provide information on the role of Rho, a GTP-binding protein, in postnatal development of the brain cells, the change in the levels of Rho protein and Rho-related proteins was examined in the brain of mice for two weeks after birth, in parallel with the changes in the activity of marker enzymes for neuronal and glial cells. The activities of acetylcholine esterase and choline acetyltransferase of whole brain homogenate, both of which are neuronal marker enzymes, were progressively increased in an age-dependent manner. The activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase, a glial marker enzyme, increased markedly between one and two weeks after birth. In contrast, the levels of RhoA and RhoB in the membrane fraction were decreased during the postnatal period. The amount of Rho GDP dissociation inhibitor, a regulatory protein for Rho, was unchanged, while those of Rho target proteins, Rock-2 and citron, were gradually increased. Since the inactivation of Rho is known to induce neurite extension and neuronal and glial differentiation in vitro, our results suggest that the Rho signalling pathway plays a regulatory role in the postnatal differentiation of neuronal and glial cells in vivo.
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PMID:Postnatal changes in Rho and Rho-related proteins in the mouse brain. 1084 19

As an extension of a previous validation study, the concentration-dependent effects of a series of anticonvulsant drugs were examined in aggregating cell cultures of foetal rat telencephalon. Cultures were treated either at an early (day 5 to day 14) or at an advanced (day 20 to day 28) developmental stage, and assayed for changes in the activities of the cell type-specific enzymes choline acetyltransferase (ChAT), acetylcholinesterase (AChE), glutamic acid decarboxylase (GAD), glutamine synthetase (GS) and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP). Five drugs (carbamazepine, diazepam, phenobarbital, phenytoin and valproate), currently used in the treatment of epileptic patients, were tested together with losigamone, a recently developed anticonvulsant. The results show distinct, concentration-dependent patterns of biochemical changes for the different drugs. Phenytoin, carbamazepine, losigamone and diazepam greatly reduced GAD, ChAT and AChE activities, indicating a relatively high neuron-specific toxic potential. Diazepam produced a more general pattern of toxicity and, in contrast to the anticonvulsants, showed higher toxicity in less-differentiated cultures. Phenobarbital and valproate slightly but significantly increased the activities of several enzymes. The patterns of concentration-dependent effects observed in this three-dimensional cell culture system are in good agreement with the presumed neurotoxic and/or teratogenic potential of these drugs.
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PMID:Anticonvulsant drug toxicity in rat brain cell aggregate cultures. 2065 Jan 3


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