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:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A massive and transitory increase in c-fos mRNA and Fos protein occurred in rats intoxicated by a single dose of soman (organophosphate compound and irreversible cholinesterase inhibitor) only in animals that had seizures. Comparison of immunohistochemistry that localizes Fos protein and of in situ hybridization that localizes its mRNA showed that there was an early and explosive expression of mRNA in many cerebral regions followed by transitory immunoreactivity in only some regions (piriform cortex, entorhinal area, hippocampus). The levels of mRNA and c-fos-like immunoreactivity decreased slowly and returned to basal level 24 h after soman administration.
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PMID:Variation in the expression of c-fos after intoxication by soman. Comparative study using in situ hybridization and immunohistochemistry. 845 76

Sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, causes increased levels of tyrosine phosphorylation and blocks, at noncytotoxic concentrations, the differentiative response of rat pheochromocytoma (PC12) cells to beta-nerve growth factor (beta NGF) and basic fibroblast growth factor (bFGF) in a reversible manner. It also prevents growth factor-induced neurite proliferation in primed cells and causes the retraction of previously formed neurites, even in the presence of beta NGF or bFGF. It is equally effective in blocking neurite proliferation by 8-Br-cAMP. Zinc chloride and ammonium molybdate, two other inhibitors of tyrosine phosphatases, also cause parallel decreases in neurite proliferation. Orthovanadate generally reduces the transcription of immediate early response genes (TIS 8 and c-fos) and secondary response genes (ornithine decarboxylase (ODC), acetyl-cholinesterase (AChE) and SCG 10) induced by beta NGF, bFGF, EGF, and PMA, albeit in a variable fashion. There was no observed effect on the kinetics of expression as judged by TIS 8 induction by beta NGF and protein kinase C (PKC) downregulation did not change the levels of inhibition by orthovanadate seen in control cells. Orthovanadate does not affect the production of diacylglycerol induced by beta NGF or bFGF. These observations are consistent with the view that growth factor stimulation of differentiation in PC12 cells involves at least one other PKC independent pathway, and that cAMP and PMA (and their active analogs) activate tyrosine kinases (albeit probably secondarily), which are at least partially responsible for their actions. Although the exact site(s) of action of orthovanadate that lead to the inhibition of growth factor-induced neurite proliferation are unknown, the results presented suggest that it prolongs tyrosine phosphorylations by nonreceptor tyrosine kinases that act downstream from the receptor kinases.
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PMID:Effect of nerve growth factor and fibroblast growth factor on PC12 cells: inhibition by orthovanadate. 846 55

To understand the mechanism underlying the neurotoxicity of lithium ion, we investigated the inhibition of the nerve growth factor-induced neuronal differentiation of rat PC12 pheochromocytoma cells induced by treatment with LiCl. Incubation with 0.1-3 mM LiCl from 30 min before nerve growth factor (NGF) treatment attenuated neurite outgrowth. Moreover, incubation with 3 mM LiCl from 24 h before strongly reduced the neurite out-growth. The chronic pretreatment inhibited the NGF-caused induction of acetyl-cholinesterase activity known to be elevated by NGF in transcription-dependent processes, and inhibited expression of c-fos proto-oncogene mRNA. This pretreatment also inhibited the NGF-induced formation of inositol phosphates, accompanied by the significant accumulation of inositol monophosphate. These observations, that chronic treatment with LiCl inhibits the NGF-induced neuronal differentiation in a transcription-dependent manner and inhibits phosphoinositide metabolism, suggest a possible causal relationship between these two events.
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PMID:Characterization of inhibition by chronic treatment with lithium ion on nerve growth factor-induced neuronal differentiation of rat PC12 pheochromocytoma cells. 887 36

Pyridostigmine, a carbamate acetylcholinesterase (AChE) inhibitor, is routinely employed in the treatment of the autoimmune disease myasthenia gravis. Pyridostigmine is also recommended by most Western armies for use as pretreatment under threat of chemical warfare, because of its protective effect against organophosphate poisoning. Because of this drug's quaternary ammonium group, which prevents its penetration through the blood-brain barrier, the symptoms associated with its routine use primarily reflect perturbations in peripheral nervous system functions. Unexpectedly, under a similar regimen, pyridostigmine administration during the Persian Gulf War resulted in a greater than threefold increase in the frequency of reported central nervous system symptoms. This increase was not due to enhanced absorption (or decreased elimination) of the drug, because the inhibition efficacy of serum butyryl-cholinesterase was not modified. Because previous animal studies have shown stress-induced disruption of the blood-brain barrier, an alternative possibility was that the stress situation associated with war allowed pyridostigmine penetration into the brain. Here we report that after mice were subjected to a forced swim protocol (shown previously to simulate stress), an increase in blood-brain barrier permeability reduced the pyridostigmine dose required to inhibit mouse brain AChE activity by 50% to less than 1/100th of the usual dose. Under these conditions, peripherally administered pyridostigmine increased the brain levels of c-fos oncogene and AChE mRNAs. Moreover, in vitro exposure to pyridostigmine increased both electrical excitability and c-fos mRNA levels in brain slices, demonstrating that the observed changes could be directly induced by pyridostigmine. These findings suggest that peripherally acting drugs administered under stress may reach the brain and affect centrally controlled functions.
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PMID:Pyridostigmine brain penetration under stress enhances neuronal excitability and induces early immediate transcriptional response. 909 57

Quantitative methods of cell density, the intensities of both acetyl cholinesterase (AChE) and NADPH diaphorase (NADPHd), as well as the basal expression of c-fos, have been carried out in order to study the anatomical divisions of the medial geniculate body (MGB) and the group of nuclei located ventromedially to the MGB called the paralaminar complex (PL). The MGB was composed of the dorsal (MGd), and the ventral (MGv) divisions. We included the medial, or the magnocellular division (MGm), in the PL complex. MGd was composed of a dorsolateral (DL) core and a belt. The belt was composed of the suprageniculate (SG), the deep dorsal (DD), the caudo-medial (CM) and the caudo-dorsal (CD) nuclei. In the MGv, the basal expression of c-fos was the only way to trace a clear boundary between the ovoid (Ov) and the ventrolateral (VL) divisions. However, the marginal zone (MZ) was clearly and contrastingly different. The PL was considered to be composed of: the MGm, the posterior intralaminar nucleus (PIN), the peripeduncular nucleus (PP) and the nucleus subparafascicularis lateralis (SPFL). The MGm and the PIN share most of the chemical features, meanwhile both SPFL and PP displayed different patterns of NADPHd reactivity. The study of cell density on Giemsa stained sections confirmed main divisions of the area. AChE and NADPHd methods allowed the main MGB divisions to be discriminated. The differences between subdivisions were emphasized when cell density and c-fos activity were quantified in each nucleus. Each MGB division displayed a different pattern of c-fos activity under basal conditions. Thus, c-fos basal expression was a particular feature in each MGB or PL nucleus.
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PMID:Chemical divisions in the medial geniculate body and surrounding paralaminar nuclei of the rat: quantitative comparison of cell density, NADPH diaphorase, acetyl cholin esterase and basal expression of c-fos. 1548 1

Chlorpyrifos (CPF) is an organophosphate widely used as an insecticide in agriculture which elicits short- and long-term neurobehavioral deficits after acute administration. Because little is known about the specific brain areas targeted by CPF, investigating for the location of its neuroanatomical targets could help to describe the brain systems involved in the neurobehavioral toxicity developed in CPF-exposed organisms. To meet this objective, in the present study we evaluated CPF-induced c-fos expression. In addition, locomotor behavior and cerebral cholinesterase level were evaluated. We found two main sets of results. First, no significant c-fos expression was found in cholinoceptive regions in CPF-treated rats 2 h or 24 h post-administration, despite the fact that 41% and 62% acetylcholinesterase inhibition, respectively, were present in brain homogenates. These results are consistent with previous reports showing CPF-induced activation of adaptive neural mechanisms re-establishing cholinergic tone. Second, 24 h post-intoxication CPF elicited c-fos expression in cytokine-related areas. Cytokines have been involved in anxiety-like responses and psychiatric stress syndromes. Taking into account that CPF triggers the synthesis of peripheral cytokines, the present data stress the need to further clarify functional relations between organophosphate-triggered peripheral cytokines and emotional disturbances reported in intoxicated organisms.
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PMID:Neuroanatomical targets of the organophosphate chlorpyrifos by c-fos immunolabeling. 1565 65

The present study examined, in mice, whether regional patterns of brain monoamines concentrations (DA, 5-HT and their metabolites) and expression of c-Fos protein, that may represent a prolonged functional change in neurons, could be changed after a combined exposure to stress and the peripheral cholinesterase reversible inhibitor pyridostigmine (PYR). Animals were subjected every day to a random combination of mild unescapable electric footshocks and immobilization over a 12-day period, resulting in a significant increase of glucocorticoids levels and an activation of c-fos in hippocampus, thalamus and piriform cortex. This stress protocol induced a significant increase of 5-HT levels in striatum, hippocampus and ponto mesencephalic area (PMA) but failed to induce any DA activation. When PYR (0.2 mg/kg s.c. inducing 19-35% inhibition of the plasmatic ChE activity) was administered twice a day during the last 5 days of the stress session, 5-HIAA levels and expression of c-fos oncogene were significantly increased in the most of the brain areas studied. DA levels were also enhanced in striatum/hippocampus as a result of a possible activation of mesolimbic and nigrostriatal dopamine systems. Taken together, these results suggest that a combined exposure to certain stress conditions and PYR leads, in mice, to functional changes in neurons and may affect centrally controlled functions. The mechanisms underlying these modifications and their behavioral implications remain to be further investigated.
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PMID:Peripheral ChE inhibition modulates brain monoamines levels and c-fos oncogene in mice subjected to a stress situation. 1601 84

Exposure to either chlorpyrifos (CPS) or methyl parathion (MPS) results in the inhibition of acetylcholinesterase and leads to altered neuronal activity which normally regulates critical genes such as the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). The effects of postnatal exposure to CPS and MPS on the expression of messenger RNA (mRNA) and protein levels for NGF and BDNF were investigated in the frontal cerebral cortex (cortex) and hippocampus of rats. Oral administration of CPS (4.0 or 6.0 mg/kg), MPS (0.6 or 0.9 mg/kg), or the safflower oil vehicle was performed daily from postnatal day 10 (PND10) through PND20. Exposure induced significant effects on growth and cholinesterase activity. Increased NGF protein levels were observed in the hippocampus but not the cortex on PND20 with some reduction occurring on PND28 in both regions. These changes did not correlate with the changes in NGF mRNA. BDNF mRNA was increased in both regions on PND20 and PND28, whereas BDNF protein levels were increased on PND20. On PND12, c-fos mRNA, a marker of neuronal activation, was increased in both regions. Total BDNF protein was increased in the hippocampus but decreased in the cortex. No changes in NGF protein were observed. These results indicate that repeated developmental OP exposure during the postnatal period alters NGF and BDNF in the cortex and the hippocampus and the patterns of these alterations differ between regions.
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PMID:Alteration of neurotrophins in the hippocampus and cerebral cortex of young rats exposed to chlorpyrifos and methyl parathion. 1789 97

The ubiquitous cholinesterase (ChE) enzymes, functioning in the termination of acetylcholine mediated neural transmission, are also reported to have additional functions. Through application of siRNAs against butyrylcholinesterase (BChE) in R28 cells, a retinal cell line with pluripotent properties, a counter-regulation between ChEs was revealed. BChE knock down resulted in an up-regulation of not only acetylcholinesterase (AChE), but also altered the signaling status of PKC and ERK. Knockdown of BChE modified ERK signaling most notably through ERK1/2 proteins, together with the transcription activator P90RSK1 and c-fos. Stimulation of the R28 cell line by forskolin revealed that ChEs are involved in an intricate cross talk between different signaling pathways. Forskolin-stimulated R28 cells displayed a robust cholinergic response, as detected by both electrophysiology and ChE expression, and changed the activation status of PKC/ERK signaling pathways. The findings in R28 cells show that ChE expressions are inversely co-regulated and act through the transcription factors c-fos and P90RSK1. Since R28 cells have the capacity to differentiate into different cell types through stimulation of signaling pathways, ChEs are likely to be associated with cell fate determination, rather than just terminating cholinergic responses.
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PMID:Counter-regulation of cholinesterases: differential activation of PKC and ERK signaling in retinal cells through BChE knockdown. 2109 73

Depression is a common comorbid condition in Parkinson's disease (PD). Patients with depression have a two-fold increased risk to develop PD. Further, depression symptoms often precede motor symptoms in PD and are frequent at all stages of the disease. However, the influence of a depressive state on the responses to antiparkinson treatments is largely unknown. In this study, the genetically inbred depression-like flinders sensitive line (FSL) rats and control flinders resistant line (FRL) rats were studied in models of experimental parkinsonism. FSL rats showed a potentiated tremorgenic response to tacrine, a cholinesterase inhibitor used experimentally to induce 6 Hz resting tremor reminiscent of parkinsonian tremor. We also studied rats lesioned with 6-OHDA to induce hemiparkinsonism. No baseline differences in dopaminergic response to acute apomorphine or L-DOPA was found. However, following chronic treatment with L-DOPA, FRL rats developed sensitization of turning and abnormal involuntary movements (AIMs); these effects were counteracted by the anti-dyskinetic 5-HT_{1 A} agonist/D₂ partial agonist sarizotan. In contrast, FSL rats did not develop sensitization of turning and only minor AIMs in response to L-DOPA treatment. The roles of several non-dopamine systems underlying this discrepancy were studied. Unexpectedly, no differences of opioid neuropeptides or serotonin markers were found between FRL and FSL rats. The marked behavioral difference between the FRL and FSL rats was paralleled with the striatal expression of the established marker, c-fos, but also the GABAergic transporter (vGAT), and a hitherto unknown marker, tamalin, that is known to regulate mGluR5 receptor function and postsynaptic organization. This study demonstrates that behavioral and transcriptional responses of non-dopaminergic systems to experimental parkinsonism and L-DOPA are modified in a genetic rat model of depression.
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PMID:Non-dopaminergic Alterations in Depression-Like FSL Rats in Experimental Parkinsonism and L-DOPA Responses. 3226 3


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