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:3.4.16.2 (PCP)
3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Correlations between the chemical structures of agricultural fungicides and mRNA expression levels following exposure of Saccharomyces cerevisiae to toxic doses of thiuram, zineb, maneb, TPN, and PCP were examined. Structurally, thiuram, zineb, and maneb are dithiocarbamate fungicides, whereas TPN and PCP are not. To characterize chemical toxicity, genes expression was classified according to the functional groups used by the MIPS database. However, no correlations between the classification scheme and chemical structures were found. Hierarchical clustering of gene expression profiles was performed to characterize the effects of the five chemicals. According to this analysis the similarity of gene expression profiles depended on the similarity of chemical structures. These results suggest that DNA microarray technology has potential for predicting the major chemicals which will cause environmental toxicity and will provide information on new biomonitoring methods.
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PMID:Correlation of the structures of agricultural fungicides to gene expression in Saccharomyces cerevisiae upon exposure to toxic doses. 1285 20

The ability of the carcinogenic environmental toxin pentachlorophenol (PCP, 1) to react with DNA bases has been assessed using MS and NMR. Treatment of PCP (100 microM) with horseradish peroxidase (HRP/H(2)O(2)) or myeloperoxidase (MPx/H(2)O(2), from human leukocytes) in the presence of excess deoxyguanosine (dG, 2 mM) led to the isolation and identification of the oxygen-bonded C8-dG nucleoside adduct 4. The reaction was absolutely specific for dG; no detectable adduct(s) was observed from HRP/H(2)O(2) and PCP in the presence of deoxyadenosine, deoxycytidine, or thymidine. Formation of 4 was also specific for peroxidase activation that is known to oxidize PCP into the phenoxyl radical. Treatment of PCP/dG with rat liver microsomes (RLM) failed to generate 4; instead, an adduct derived from the benzoquinone electrophile tetrachloro-1,4-benzoquinone (chloranil) was observed in the extracted ion chromatogram from the RLM/NADPH-treated PCP/dG sample. The adduct 4 is the first structurally characterized O-bonded phenolic DNA nucleoside adduct and highlights the ambident electrophilicity of phenoxyl radicals (O- vs C-) in reaction at C8 of dG, as we have previously demonstrated that the para-chlorophenolic toxin, ochratoxin A (2), reacts at C8 of dG to give the C-bonded adduct 3 via the intermediacy of the OTA phenoxyl radical. Given that PCP is known to induce DNA adduct formation in vivo and human exposure has been linked to incidences of leukemia, the adduct 4 could play a key role in PCP-mediated carcinogenesis.
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PMID:An oxygen-bonded c8-deoxyguanosine nucleoside adduct of pentachlorophenol by peroxidase activation: evidence for ambident c8 reactivity by phenoxyl radicals. 1287 Aug 83

R6K-encoded pi protein can bind to the seven, 22 bp tandem iterons of the gamma origin. In this work, we use a variant of pi, His-pi.F107S, that is hyperactive in replication. In vitro, His-pi.F107S-dependent local DNA melting (open complex formation) occurs in the absence of host proteins (IHF/HU or DnaA) and it is positioned in the A + T-rich region adjacent to iterons. Experiments described here examine the effects of ATP, Mg2+ and temperature on the opening reaction. We show that the opening of the gamma origin can occur in the presence of ATP as well as AMP-PCP (a non-hydrolyzable ATP analog). This suggests that, for gamma origin, ATP hydrolysis may be unnecessary for open complex formation facilitated by His-pi.F107S. In the absence of ATP or Mg2+, His-pi.F107S yielded data suggestive of distortions in the iteron attributable to DNA bending rather than DNA melting. Our findings also demonstrate that ATP and pi stimulate open complex formation over a wide range of temperatures, but not at 0 degrees C. These and other results indicate that ATP and/or Mg2+ are not needed for His-pi.F107S binding to iterons and that ATP effects an allosteric change in the protein bound to gamma origin.
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PMID:pi protein- and ATP-dependent transitions from 'closed' to 'open' complexes at the gamma ori of plasmid R6K. 1453 Apr 47

Perinatal administration of the N-methyl-Dd-aspartate (NMDA) receptor antagonist phencyclidine (PCP) has been reported to produce regionally selective apoptotic cell death in the frontal cortex. The development of certain behavioral abnormalities following PCP treatment suggested that extracortical regions such as the striatum also could be affected. In this study, perinatal PCP treatment caused a marked reduction in striatal, but not hippocampal, staining for polysialic acid-neural cell adhesion molecule (PSA-NCAM), an NMDA-regulated molecule important in synaptogenesis. In order to isolate striatal influences to the cortex, this investigation was continued in vitro using corticostriatal slices. For these experiments we cultured coronal corticostriatal slices from postnatal day 7 rats. After 4 days in vitro, PCP was added for 48 h and then washed out for 24 h before harvesting the tissue. Similar to what was observed in vivo, we found that PCP treatment results in a marked reduction in striatal staining for PSA-NCAM. No change was observed in the mature form of NCAM. In striatal synaptoneurosomes, immunoblot analysis confirmed that the levels of PSA-NCAM and synaptophysin, a molecule often used as a marker of synaptogenesis, were substantially down-regulated by PCP. These effects were prevented by M40403, a superoxide dismutase mimetic that also prevented the PCP-induced terminal dUTP nick-end labeling of DNA fragments that was observed selectively in the cortex. These data suggest that PCP causes cell death by apoptosis selectively in the cortex, but not in the striatum, following either in vivo treatment of perinatal rat pups or in vitro treatment of corticostriatal slices. Further, cortical apoptosis induced by PCP negatively impacts striatal synaptogenesis, a process important in normal neural development. This deficit is probably caused by a reduction in corticostriatal neurotransmission. It is possible that the dysregulation of striatal synaptogenesis contributes to the behavioral abnormalities observed following perinatal PCP administration in vivo.
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PMID:Blockade of N-methyl-D-aspartate receptors by phencyclidine causes the loss of corticostriatal neurons. 1506 89

A dextromethorphan (3-methoxy-17-methylmorphinan) analog, dimemorfan (3-methyl-N-methylmorphinan) that is not metabolized to dextrorphan [3-hydroxy-17-methylmorphinan, which induces phencyclidine (PCP)-like behavioral effects], attenuates maximal electroshock seizures. However, the pharmacological mechanism of action of dimemorfan remains to be determined. In this study, we assessed the locomotor activity mediated by these morphinans. Circling behavior was pronounced in mice treated with PCP or dextrorphan, while animals treated with dextromethorphan exhibited moderate behaviors. Dimemorfan did not show any significant behavioral effects. We used BAY k-8644 (an L-type Ca2+ channel agonist in the dihydropyridine class) to explore the effects of dextromethorphan and dimemorfan on the convulsant activity regulated by calcium channels. Intracerebroventricular injection of BAY k-8644 (37.5 microg) significantly induced seizures in mice. As with dextromethorphan (6.25 or 12.5 mg/kg), dimemorfan (6.25 or 12.5 mg/kg) pretreatment significantly attenuated BAY k-8644-induced seizures in a dose-dependent manner. BAY k-8644-induced seizure activity paralleled increased expression of c-fos and c-jun, AP-1 DNA binding activity, and fos-related antigen immunoreactivity. Pretreatment with dextromethorphan or dimemorfan significantly attenuated the expression induced by BAY k-8644. Therefore, our results suggest that the anticonvulsant effects of dextromethorphan and dimemorfan are mediated, at least in part, via L-type calcium channel, and that dimemorfan is equipotent to dextromethorphan in preventing BAY k-8644-induced seizures, while it lacks behavioral side effects related to psychotomimetic reactions.
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PMID:Dimemorfan prevents seizures induced by the L-type calcium channel activator BAY k-8644 in mice. 1508 42

TCHQ is a major carcinogenic metabolite of the widely used wood preservative PCP. Recently, we found that TCHQ was a promoter in a mouse skin carcinogenesis model. However, the mechanism is still not clear. In this study, we showed that overexpression of Bcl-2 effectively suppressed TCHQ-induced apoptosis in NIH3T3 cells, as evidenced by morphological changes and DNA fragmentation. Although production of ROS contributes to TCHQ-induced apoptosis, Bcl-2 failed to attenuate TCHQ-elicited increase of intracellular ROS level. In addition, overexpressed Bcl-2 provides only partial protection against TCHQ-induced cellular DNA damage. We also found that TCHQ induced a change in mitochondrial transmembrane potential, and that caspase-9 and subsequent caspase-3 can be activated during TCHQ-induced acute apoptosis. Interestingly, TCHQ induced a significant upregulation of Bcl-2 expression, and over-expressed Bcl-2 can dramatically inhibit the change of mitochondria membrane potential and activation of both caspase-9 and -3. Thus, our results suggest TCHQ-induced tumor promotion may be through a mechanism of upregulation of Bcl-2 protein and subsequent apoptosis inhibition.
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PMID:Bcl-2 overexpression inhibits tetrachlorohydroquinone-induced apoptosis in NIH3T3 cells: a possible mechanism for tumor promotion. 1510 27

Phencyclidine (PCP) is an N-methyl-D-aspartate receptor (NMDAR) antagonist known to cause selective neurotoxicity in the cortex following subchronic administration. The purpose of this study was to test the hypothesis that upregulation of the NMDAR plays a role in PCP-induced apoptotic cell death. Corticostriatal slice cultures were used to determine the effects of NMDAR subunit antisense oligodeoxynucleotides (ODNs) on PCP-induced apoptosis and NMDAR upregulation. NR1, NR2A or NR2B antisense ODNs were incubated alone or with PCP for 48h. One day following washout, it was observed that PCP treatment caused an increase in NR1, NR2A and Bax polypeptides in the cortex, but had no effect on Bcl-xL. These increases were associated with an increase in cortical histone-associated DNA fragments. Co-incubation of PCP with either NR1 or NR2A antisense significantly reduced PCP-induced apoptosis, while neither NR2B antisense ODN nor NR1 sense ODN used as a control had an effect. This effect was exactly correlated with the ability of the antisense ODNs to prevent PCP-induced upregulation of NR subunit proteins and the pro-apoptotic protein, Bax. That is, western analysis showed that antisense ODNs directed against either NR1 or NR2A prevented PCP-induced increases in Bax in addition to preventing the upregulation of the respective receptor proteins. On the other hand, the NR2B antisense ODN had no effect on either NR2B protein or on Bax. These data suggest that NR1 and NR2A antisense ODNs offer neuroprotection from apoptosis, and that upregulation of the NR1 and NR2A subunits following PCP administration is at least partly responsible for the observed apoptotic DNA fragmentation.
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PMID:The role of NMDA receptor upregulation in phencyclidine-induced cortical apoptosis in organotypic culture. 1582 8

To study the method for Rhesus box test and its significance, the sequence specific primers of upstream, downstream and hybrid Rhesus boxes were designed according to RhD gene sequence; the upstream, downstream and hybrid Rhesus boxes were determined by PCP-SSP and mismatched PCR. The results showed that this method was confirmed by DNA Standard test. It was shown that in unrelative RhD positive individuals RHD(+)/RHD(-), RHD(+)/RHD(+) genotype accounted for 9.00%, 91.00% respectively, and in RhD negative individuals RHD(+)/RHD(-), RHD(+)/RHD(+), RHD(-)/RHD(-) genotype were 26.14%, 3.92%, 69.94% respectively. It is concluded that the method of Rhesus box test was confirmed to be reliable and can be used for the identification of RhD haplotype gene structure, as well as for study on inheritance, clinical transfusion and neonatal hemolytic diseases.
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PMID:[A method for Rhesus box test]. 1640 90

Amphetamine (AMPH) and phencyclidine (PCP) induce a variety of behavioural and synaptic changes in the brain, many of which are believed to involve the regulation of gene expression. In this study, we examined the effects of AMPH (5mg/kg), PCP (5mg/kg) and their combination (5mg/kg each) on rat motor activity as well as on the activation of the AP-1 transcription factor in rat brains. AMPH administration, followed by PCP, led to a statistically significant elevation of locomotor activity. It was found that the behavioural response of rats was more pronounced when the two drugs were administered together. The electrophoretic mobility shift assay (EMSA) revealed a significant increase in AP-1-binding activity after treatments with AMPH, PCP or their combination. Super shift/shift inhibition analysis demonstrated the presence of c-Fos and c-Jun protein families in the transcriptional complex bound to AP-1 sequences. Further, our results suggest that the enhanced behavioural changes after AMPH and PCP administration were associated with increased expression of AP-1 proteins (Fos and Jun) in the cortex, striatum and hippocampus and that their binding to AP-1 sites on the DNA contributes to long-term changes in rat brain.
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PMID:Enhancement of AP-1 DNA-binding activity during amphetamine- and phencyclidine-mediated behaviour in rats. 1667 66

In bacteria, the initiation of replication is controlled by DnaA, a member of the ATPases associated with various cellular activities (AAA+) protein superfamily. ATP binding allows DnaA to transition from a monomeric state into a large oligomeric complex that remodels replication origins, triggers duplex melting and facilitates replisome assembly. The crystal structure of AMP-PCP-bound DnaA reveals a right-handed superhelix defined by specific protein-ATP interactions. The observed quaternary structure of DnaA, along with topology footprint assays, indicates that a right-handed DNA wrap is formed around the initiation nucleoprotein complex. This model clarifies how DnaA engages and unwinds bacterial origins and suggests that additional, regulatory AAA+ proteins engage DnaA at filament ends. Eukaryotic and archaeal initiators also have the structural elements that promote open-helix formation, indicating that a spiral, open-ring AAA+ assembly forms the core element of initiators in all domains of life.
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PMID:Structural basis for ATP-dependent DnaA assembly and replication-origin remodeling. 1688 4


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