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)

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.
 ...
PMID:Effect of short-term exposure to hexachlorophene on rat brain cell specific marker enzymes. 290 23

A rat brain P3 fraction enriched in ER derived microsomes was centrifuged through a 20-40% linear sucrose gradient in a Beckman Ti-14 Zonal rotor and 11 fractions were obtained. The distribution of marker enzyme activities and protein were determined in these 11 subfractions. NADPH-Cytochrome C reductase, choline phosphotransferase were employed for endoplasmic reticulum, Na+,K+-ATPase, 5'-nucleotidase, and acetylcholinesterase were employed for plasma membrane, 2',3'-cyclic nucleotide phosphohydrolase was employed for myelin. The bulk of the protein was recovered in the 24-34% sucrose fractions, Na+,K+-ATPase, 5'-nucleotidase, and acetylcholinesterase were in the 22-38% sucrose fractions while NADPH-cytochrome C reductase and CNPase were enriched in the 20-22% sucrose fractions. The ethanolamine and the serine base exchange activities had a bimodal distribution, with highest specific activities in sucrose fractions 32-34% and 20-24%. Choline base exchange activity was nearly undetectable in all the fractions. The specific activities of CDP-choline phosphotransferase, and phospholipid-N-methyltransferase were highest in the 20-22% sucrose fraction. Phospholipid-N-methyltransferase activity was significantly stimulated in the presence of exogenous phospholipid acceptors as phosphatidylethanolamine or phosphatidylmonomethylethanolamine or phosphatidyldimethylethanolamine, however, the greatest response was with phosphatidylmonomethylethanolamine. The rat brain P3 fraction yielded a population of a membrane at the light end of the sucrose gradient which has a buoyant density similar to myelin but seemed to be enriched with NADPH cytochrome C reductase and phospholipid modifying enzymes. This is in contrast to liver microsomes submitted to a similar fractionation.
 ...
PMID:Distribution of selected phospholipid modifying enzymes in rat brain microsomal subfractions prepared by density gradient zonal rotor centrifugation. 298 22

The enzymatic activities in post-mortem rat brain kept at 4 degrees C and at 25 degrees C were determined for a number of enzymes localized in specific cell types in the central nervous system. Choline acetyltransferase (CAT), glycerol-3-phosphate dehydrogenase (GPDH), glutamine synthetase (GS), lactate dehydrogenase (LDH) and 2',3'-cyclic nucleotide phosphohydrolase (CNPase) were found to be very stable at both 4 degrees C and 25 degrees C with only slight, if any, losses of activity being seen even at periods as long as 72 hr. Glutamic acid decarboxylase (GAD) activity was less stable than that of the other enzymes. In brains kept at 4 degrees C GAD activity was stable out to 24 hr after which it began to decline rapidly to 65% of control at 72 hr. In brains kept at 25 degrees C, GAD activity was stable for 6-8 hr and then began to steadily decline to 58% of control at 24 hr and 29% of control at 72 hr. Assuming that these enzymes have similar stabilities in post-mortem human brain, the effect of post-mortem delay in processing tissues may be of lesser significance than other factors with regard to the measured enzyme activities in human brain samples.
 ...
PMID:Stability of neuronal and glial marker enzymes in post-mortem rat brain. 301 Jan 49

The metabolism of thyroxine (T4) and triiodothyronine (T3) in cultured glial cells was studied in situ. Cultures were prepared from fetal rat brain and grown for the last 4 days in a chemically defined medium (CDM). They contained astrocytes and oligodendrocytes as shown by the enzyme markers, glutamine synthetase and 2',3'-cyclic nucleotide phosphohydrolase. These cells contained high affinity (22-33 pM), limited capacity (120-230 fmol/mg DNA) nuclear receptors for T3. Cells incubated in situ with 50 pM [125I]T4 actively metabolized the hormone. The major iodothyronine produced was T3 (220-570 fmol/4 h/mg DNA). About 70% accumulated in the cells, the remainder was released into the medium. Within the cells, T3 was partly bound to the nuclear receptors (16.5-20 fmol/mg DNA). Reverse T3 (rT3) was a minor metabolite (30-45 fmol/4 h/mg DNA); it was almost completely released into the medium. The half-life of [125I]T3 (50 pM) was found to be about 15 h. These results show that, in situ, glial cell cultures containing astrocytes and oligodendrocytes grown in CDM actively deiodinate T4 to T3 and degrade T3 rather slowly.
 ...
PMID:Thyroid hormone metabolism by glial cells in primary culture. 380 6

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.
 ...
PMID:The influence of systemic factors on acrylamide-induced changes in brain, nerve, and other tissues. 608 44

Four enzymes related to specific cell functions were assayed in rat sciatic nerve injury by crush (cr) or crush and ligation (cr-lig) after 2, 7, and 15 days in situ. Enzyme activities in segments of sciatic nerve proximal and distal to the injury were compared to those in corresponding segments of the contralateral nerve. Choline acetyltransferase (CAT) activity in the distal portion decreased by 65% for cr and almost to zero for cr-lig by day 7, while in the proximal portions CAT decreased to 70% of control values by 7 days and to 50% at 15 days after cr-lig. The activity of the Schwann cell-myelin-associated enzyme 2',3'-cyclic nucleotide phosphohydrolase (CNP) decreased slowly distal to the injury. Distal to both types of injury the lysosomal enzyme beta-glucuronidase (GLR) increased six- to eightfold by 15 days. Proximal to injury GLR also increased (P cr X 2.5, P cr-lig X 5) but the peak proximally was attained by day 7. Despite interruption of axonally transported enzymes, the activities of the metabolic enzyme creatine kinase (CK) increased distal to injury apparently reflecting changes in the functions of the Schwann cells. The loss of metabolic enzymes from the axonal compartment may be completely obscured by reciprocal changes in the non-neuronal compartments if the activity is present in both compartments.
 ...
PMID:Enzyme changes in axon, myelin, and Schwann cells in injured sciatic nerve. 631 Jan 39

The effects of glia maturation factor (GMF) on cell proliferation and differentiation were investigated with 3 astroglioma cells (GE-12, C6, and GA-1), Schwannoma-like cells (354A), and mixed glioma cells (LRM-55). In the exponentially growing phase the growth rates of all glioma cells were enhanced by GMF regardless of the presence or absence of serum, but the factor failed to make the saturation density surpass the control level observed in the medium without GMF even in the chemically defined medium (N2 medium). GMF markedly lowered the saturation density of Schwannoma-like cells in N2 medium. Although GMF increased the intracellular content of S-100 protein 10-fold and 2',3'-cyclic nucleotide phosphohydrolase activity 1.5-fold in Schwannoma-like cells, GMF conversely decreased the S-100 contents and glycerol phosphate dehydrogenase activity in astroglioma cells. All the astroglioma cells secreted into the culture medium large quantities of a growth-promoting factor(s) which had similar chemical properties to those of GMF and stimulated the proliferation of normal glioblasts; but Schwannoma-like cells did not, although they produced a small amount of such a factor(s). These findings imply that astroglioma cells are deprived of the differentiation-promoting response to GMF while Schwannoma-like cells still preserve the response in addition to the proliferative response to GMF.
 ...
PMID:The absence of differentiation-promoting response of astroglioma cells to glia maturation factor. 632 49

The incorporation of 35SO4(2-) and [3H]galactose into myelin-associated lipids, the activity of enzymes catalyzing the synthesis of these lipids, and the activity of 2',3'-cyclic nucleotide phosphohydrolase were determined in primary cultures of dissociated cells from brains of 15-day embryonic mice. These biochemical parameters of myelination were barely detectable before about 10 days in culture, but their activity increased in parallel after this time and reached a maximum at about 40 days in culture. The activities of the selected enzymes in homogenates of the cultured cells at their optimum age were of the same order of magnitude as the same enzymes derived from fresh brain. Scanning electron microscopic studies showed that the cells after adhering to the surface by the 4th day form aggregates and extensive membranes; the aggregates increase in size and coalesce to form nests of cells by the 15th day; the surface of the aggregates becomes smoother until by the 43rd day the entire surface is covered by and cells are buried in a membrane-like substance. These biochemical measurements and morphological data suggest that the cultures of dissociated cells from brain of 15 day embryonic mice provide a useful system for studying myelination and its regulation in vitro.
 ...
PMID:Investigations on myelination in vitro: biochemical and morphological changes in cultures of dissociated brain cells from embryonic mice. 736 98

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.
 ...
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.
 ...
PMID:Effects of hypoxia on oligodendrocyte signal transduction. 768 39


<< Previous 1 2 3 4 Next >>