Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CATECHOL”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed2006

Regulation of catechol-O-methyltransferase expression in human myometrial cells.

OBJECTIVE: The catechol-O-methyltransferase enzyme catalyzes the methylation of the catechol estrogens, 2- or 4-hydroxyestrogen, to 2- or 4-methoxyestrogen. Both the hydroxy estrogens and methoxy estrogens were shown to modulate the effects of estrogen. Because catechol-O-methyltransferase activity controls levels of these metabolites, it may help regulate the cellular estrogenic milieu. In this study, we examined the regulation of catechol-O-methyltransferase expression in human myometrial cells. METHODS: Catechol-O-methyltransferase expression was assessed by reverse transcription-polymerase chain reaction, Western blot, and luciferase assays in human myometrial cells after treatment with estrogen or progesterone. Catechol-O-methyltransferase expression was measured in cells after treatment with tumor necrosis factor alpha (TNFalpha) alone or with lactacystin, a proteasome inhibitor. Luciferase assays were also conducted using human myometrial cells containing an estrogen response element-luciferase reporter gene to measure levels of estrogen-mediated transactivation after treatment with estrogen and increasing concentrations of 2-hydroxestrogen. RESULTS: Catechol-O-methyltransferase expression was down-regulated by progesterone or estrogen. Tumor necrosis factor alpha upregulated catechol-O-methyltransferase expression, whereas cotreatment with lactacystin attenuated this response, suggesting that TNFalpha activated nuclear factor kappa B to induce catechol-O-methyltransferase expression. Increased concentrations of 2-hydroxyestrogen attenuated estrogen-mediated transcription in the myometrial cells. CONCLUSION: Catechol-O-methyltransferase expression may be regulated in the myometrium to control the local action of estrogen. Low levels of catechol-O-methyltransferase in the myometrium would result in an accumulation of 2-hydroxyestrogen and may antagonize the local effect of estrogen. High levels of catechol-O-methyltransferase in the myometrium would result in lower levels of 2-hydroxyestrogen and may increase sensitivity to estrogen.

Acetylcysteine↗
PubMed2006

Differential gene expression in response to phenol and catechol reveals different metabolic activities for the degradation of aromatic compounds in Bacillus subtilis.

Aromatic organic compounds that are present in the environment can have toxic effects or provide carbon sources for bacteria. We report here the global response of Bacillus subtilis 168 to phenol and catechol using proteome and transcriptome analyses. Phenol induced the HrcA, sigmaB and CtsR heat-shock regulons as well as the Spx disulfide stress regulon. Catechol caused the activation of the HrcA and CtsR heat-shock regulons and a thiol-specific oxidative stress response involving the Spx, PerR and FurR regulons but no induction of the sigmaB regulon. The most surprising result was that several catabolite-controlled genes are derepressed by catechol, even if glucose is taken up under these conditions. This derepression of the carbon catabolite control was dependent on the glucose concentration in the medium, as glucose excess increased the derepression of the CcpA-dependent lichenin utilization licBCAH operon and the ribose metabolism rbsRKDACB operon by catechol. Growth and viability experiments with catechol as sole carbon source suggested that B. subtilis is not able to utilize catechol as a carbon-energy source. In addition, the microarray results revealed the very strong induction of the yfiDE operon by catechol of which the yfiE gene shares similarities to glyoxalases/bleomycin resistance proteins/extradiol dioxygenases. Using recombinant His6-YfiE(Bs) we demonstrate that YfiE shows catechol-2,3-dioxygenase activity in the presence of catechol as the metabolite 2-hydroxymuconic semialdehyde was measured. Furthermore, both genes of the yfiDE operon are essential for the growth and viability of B. subtilis in the presence of catechol. Thus, our studies revealed that the catechol-2,3-dioxygenase YfiE is the key enzyme of a meta cleavage pathway in B. subtilis involved in the catabolism of catechol.

Bacillus subtilis↗
PubMed2005

Catechol sensor using poly(aniline-co-o-aminophenol) as an electron transfer mediator.

In this work, poly(aniline-co-o-aminophenol) (copolymer) was used as an electron transfer mediator in the electrochemical oxidation of catechol due to its reversible redox over a wide range of pH. The experimental results indicate that the anodic peak potential of catechol at the copolymer electrode is lower than that at the platinum electrode in a solution consisting of catechol and sodium sulfate with pH 5.0, and the activation energy for the electrochemical oxidation of catechol at the copolymer electrode is low (23.6 kJ mol(-1)). These are strong evidence for the electrocatalytic oxidation of catechol at the copolymer electrode. The -OH group on the copolymer chain plays an important role in the electron transfer between the copolymer electrode and catechol in the solution. Based on the catalytic oxidation, the copolymer is used as a sensor to determine the concentration of catechol. The response current of the sensor depends on the concentration of catechol, pH, applied potential and temperature. At 0.55 V (versus saturated calomel reference electrode (SCE)) and pH 5.0, the sensor has a fast response (about 10s) to catechol and good operational stability. The sensor shows a linear response range between 5 and 80 microM catechol with a correlation coefficient of 0.997. It was found that phenol and resorcinol cannot be oxidized at the copolymer electrode at potentials < or =0.55 V, so controlling the sensor potential affords a good way of avoiding the effect of phenol and resorcinol on the determination of catechol.

Aminophenols↗
PubMed2005

Benzene-free synthesis of catechol: interfacing microbial and chemical catalysis.

The toxicity of aromatics frequently limits the yields of their microbial synthesis. For example, the 5% yield of catechol synthesized from glucose by Escherichia coli WN1/pWL1.290A under fermentor-controlled conditions reflects catechol's microbial toxicity. Use of in situ resin-based extraction to reduce catechol's concentration in culture medium and thereby its microbial toxicity during its synthesis from glucose by E. coli WN1/pWL1.290A led to a 7% yield of catechol. Interfacing microbial with chemical synthesis was then explored where glucose was microbially converted into a nontoxic intermediate followed by chemical conversion of this intermediate into catechol. Intermediates examined include 3-dehydroquinate, 3-dehydroshikimate, and protocatechuate. 3-Dehydroquinate and 3-dehydroshikimate synthesized, respectively, by E. coli QP1.1/pJY1.216A and E. coli KL3/pJY1.216A from glucose were extracted and then reacted in water heated at 290 degrees C to afford catechol in overall yields from glucose of 10% and 26%, respectively. The problematic extraction of these catechol precursors from culture medium was subsequently circumvented by high-yielding chemical dehydration of 3-dehydroquinate and 3-dehydroshikimate in culture medium followed by extraction of the resulting protocatechuate. After reaction of protocatechuate in water heated at 290 degrees C, the overall yields of catechol synthesized from glucose via chemical dehydration of 3-dehydroquinate and chemical dehydration of 3-dehydroshikimate were, respectively, 25% and 30%. Direct synthesis of protocatechuate from glucose using E. coli KL3/pWL2.46B followed by its extraction and chemical decarboxylation in water gave a 24% overall yield of catechol from glucose. In situ resin-based extraction of protocatechaute synthesized by E. coli KL3/pWL2.46B followed by chemical decarboxylation of this catechol percursor was then examined. This employment of both strategies for dealing with the microbial toxicity of aromatic products led to the highest overall yield with catechol synthesized in 43% overall yield from glucose.

Catechols↗
PubMed2002

Characterization of catechol glucuronidation in rat liver.

Catechols are a class of substances from natural or synthetic origin that contain a 1,2-dihydroxybenzene group. We have characterized the glucuronidation by rat liver microsomes and by the rat liver recombinant UDP-glucuronosyltransferase isoforms UGT1A6 and UGT2B1 of a series of 42 structurally diverse catechols, including neurotransmitters, polyphenols, drugs, and catechol estrogens. Small catechols (4-nitrocatechol, 2,3-dihydroxybenzaldehyde, 4-methylcatechol, and tetrachlorocatechol), tyrphostine A23, and octylgallate were glucuronidated at the highest rate by rat liver microsomes and the recombinant enzymes. By contrast, polyphenols from green tea (catechin and related compounds), 3,5-dinitrocatechol, the catechol-O-methyltransferase inhibitor drugs (entacapone, nitecapone, and tolcapone), the carboxyl catechols (gallic acid and dihydroxybenzoic acid derivatives), and the neurotransmitters and dopaminergic drugs, except dobutamine, were glucuronidated at low rate. Glucuronidation of most catechols was increased upon treatment of rats by 3-methylcholanthrene (3-MC) or Aroclor 1254. No induction was observed after administration of phenobarbital and clofibrate or treatment with catechols. Partial least-squares modeling was carried out to explain the variations of glucuronidation activity by liver microsomes of nontreated and 3-MC-treated rats. The model developed explained 82% and predicted 61% of the variations of glucuronidation activities. Among the 17 electronic and substructure parameters used that characterize the catechols, the hydrophobicity/molar volume ratio of catechols showed a strong positive correlation with the glucuronidation rate. The effect of the pK(a) of the catechol group was modeled to be nonlinear, the optimal pK(a) value for glucuronidation being between 8 and 9. Hydrogen bonding and steric effects also were important to account for to predict the glucuronidation rates.

Animals↗
PubMed1999

Endogenous catechol thioethers may be pro-oxidant or antioxidant.

Increased catechol thioether formation is associated with Parkinson's disease. In this study, we examined whether catechol thioethers, having a lower oxidation potential than their parent catechols, would cause greater oxidative damage than their parent catechols. We synthesized 5'-S-glutathionyl, cysteinyl, and N-acetylcysteinyl derivatives of dopamine and dopac, encompassing the known catechol thioethers of the mercapturate pathway. Cyclic voltametry studies showed that catechol thioethers had higher reduction potentials than their parent catechols. A higher reduction potential did not correlate with an increase in oxidative damage, measured by metal-catalyzed DNA strand breakage. 5'-S-Glutathionyldopamine and the cysteinyl adducts of dopamine and dopac mediated less oxidative damage than their parent catechols. In contrast, both N-acetylcysteinyl analogs were equipotent to dopamine. Oxygen consumption corresponded to DNA damage except for 5'-S-glutathionyldopamine. The glutathionyl and cysteinyl adducts of dopamine inhibited dopamine-mediated DNA damage indicating that these adducts may have antioxidant properties. 5'-S-Glutathionyldopamine potentiated H2O2-mediated damage whereas 5-S-cysteinyldopamine was inhibitory. Our results show that the ability of catechol thioethers to cause oxidative damage in vitro is not based simply upon the reduction potential but rather, reflects a complex relationship among structures of the parent catechol and thiol adduct, metal catalyst, and oxidant.

Antioxidants↗
PubMed1990

Human liver catechol-O-methyltransferase pharmacogenetics.

Catechol-O-methyltransferase activity and thermal stability in the human red blood cell are controlled by a common genetic polymorphism. Approximately 25% to 30% of a randomly selected population sample is homozygous for the traits of low catechol-O-methyltransferase activity and thermolabile enzyme in the red blood cell. We tested the hypothesis that the catechol-O-methyltransferase genetic polymorphism might also control those same characteristics of the enzyme in an important human drug-metabolizing organ, the liver. Catechol-O-methyltransferase enzyme activity and thermal stability were measured in 99 hepatic biopsy samples obtained during clinically indicated surgery. The frequency distribution of heated/control ratios, a measure of enzyme thermal stability, was bimodal, with 28% of samples included in a subgroup with thermolabile enzyme. There were no sex-related differences in hepatic catechol-O-methyltransferase thermal stability. However, catechol-O-methyltransferase enzyme activity in hepatic tissue from male subjects was significantly higher than that in samples from female subjects: 61.3 +/- 20.2 units/mg protein (mean +/- SD; n = 50) versus 46.6 +/- 22.2 units/mg protein (n = 49; p = 0.0002). There was a significant correlation of hepatic catechol-O-methyltransferase activity and thermal stability in samples from both female (rs = 0.698; p = 0.0001) and male subjects (rs = 0.429; p = 0.002). Finally, when both red blood cell catechol-O-methyltransferase activity and thermal stability were measured in blood samples from 34 of these patients, there was a significant correlation between catechol-O-methyltransferase heated/control ratios and levels of enzyme activity in hepatic tissue and in red blood cell lysates. These findings indicate that the genetic polymorphism that controls catechol-O-methyltransferase activity level and thermal stability in red blood cells also controls those same properties of the enzyme in the human liver.

Adolescent↗
PubMed2001

Chemical properties of catechols and their molecular modes of toxic action in cells, from microorganisms to mammals.

Catechols can undergo a variety of chemical reactions. In this review, we particularly focus on complex formations and the redox chemistry of catechols, which play an inportant role in the toxicity of catechols. In the presence of heavy metals, such as iron or copper, stable complexes can be formed. In the presence of oxidizing agents, catechols can be oxidized to semiquinone radicals and in a next step to o-benzoquinones. Heavy metals may catalyse redox reactions in which catechols are involved. Further chemical properties like the acidity constant and the lipophilicity of different catechols are shortly described as well. As a consequence of the chemical properties and the chemical reactions of catechols, many different reactions can occur with biomolecules such as DNA, proteins and membranes, ultimately leading to non-repairable damage. Reactions with nucleic acids such as adduct formation and strand breaks are discussed among others. Interactions with proteins causing protein and enzyme inactivation are described. The membrane-catechol interactions discussed here are lipid peroxidation and uncoupling. The deleterious effect of the interactions between catechols and the different biomolecules is discussed in the context of the observed toxicities, caused by catechols.

Animals↗
PubMed1986

Effects of the co-carcinogen catechol on benzo[a]pyrene metabolism and DNA adduct formation in mouse skin.

We have studied the effects of the co-carcinogen catechol (1,2-dihydroxybenzene) on the metabolic activation of [3H] benzo[a]pyrene (BaP) in mouse skin, in vivo and on the binding of BaP metabolites to DNA and protein at intervals from 0.5-24 h. Upon topical application of 0.015 mg [3H]BaP and 0.25 or 0.5 mg catechol per mouse, catechol had little effect on the total amount of [3H]BaP metabolized in mouse skin, but it affected the relative proportions of [3H]BaP metabolites. Catechol (0.5 mg/mouse) decreased the proportion of water-soluble [3H]BaP metabolites, ethyl acetate-soluble polar metabolites and quinones, but doubled the levels of unconjugated 3-hydroxy-BaP at all measured intervals after treatment. Catechol also caused a small increase in the levels of trans-7,8-dihydroxy-7,8-dihydroBaP and trans-9,10-dihydroxy-9,10-dihydroBaP 0.5 h after treatment. Two hours after treatment, the levels of these metabolites subsided to those of the controls. Catechol did not affect the levels of glutathione conjugates of BaP. However, it caused a decrease in glucuronide and sulphate conjugate formation from BaP. Catechol caused an approximately 2-fold increase in the formation of anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydroBaP (BPDE) DNA adducts and elevated the ratio of anti-syn-BPDE-DNA adducts 1.6 to 2.9-fold. Catechol treatment increased the radioactivity associated with epidermal proteins after [3H]BaP application. Because catechol increased levels of 3-hydroxyBaP, we considered the possibility that 3-hydroxyBaP might enhance the tumor initiating activities of BaP or BPDE in mouse skin; a bioassay demonstrated that this was not the case. The results of this study indicate that one important effect of catechol related to its co-carcinogenicity is its ability to enhance formation of anti-BPDE-DNA adducts in mouse skin.

Animals↗
PubMed2004

Plasma etoposide catechol increases in pediatric patients undergoing multiple-day chemotherapy with etoposide.

PURPOSE: The purpose of this research was to determine inter- and intrapatient differences in the pharmacokinetic profiles of etoposide and its genotoxic catechol metabolite during conventional multiple-day dosing of etoposide in pediatric patients. EXPERIMENTAL DESIGN: Seven pediatric patients with various malignancies received etoposide at a dose of 100 mg/m(2) i.v. over 1 h daily for 5 days. Blood samples were taken at selected time points on days 1 and 5. Plasma and protein-free plasma concentrations of etoposide and etoposide catechol were determined using a validated liquid chromatography/tandem mass spectrometry assay. Pharmacokinetic parameters of both etoposide and etoposide catechol were calculated using the WinSAAM modeling program developed at NIH. RESULTS: The mean maximum concentration (C(max)) for total (0.262 +/- 0.107 micro g/ml) and free catechol (0.0186 +/- 0.0082 micro g/ml) on day 5 were higher than the mean C(max) for total (0.114 +/- 0.028 micro g/ml) and free catechol (0.0120 +/- 0.0091 micro g/ml) on day 1. The mean area under the plasma concentration-time curve (AUC)(24h) for total (105.4 +/- 49.1 micro g.min/ml) and free catechol (4.89 +/- 2.23 micro g x min/ml) on day 5 were much greater (P < 0.05) than those for total (55.9 +/- 16.1 micro g x min/ml) and free catechol (3.04 +/- 1.04 micro g x min/ml) on day 1. In contrast, the AUC(24h) for etoposide was slightly lower on day 5 than on day 1. CONCLUSIONS: The C(max) and AUC(24h) for etoposide catechol were significantly higher on day 5 than on day 1. This suggests that metabolism of etoposide to its catechol metabolite increases in pediatric patients receiving multiple-day bolus etoposide infusions. These findings may be relevant to future reduction of the risk of leukemia as a treatment complication, because etoposide and etoposide catechol are both genotoxins.

Adolescent↗
PubMed1999

Purification and spectroscopic studies on catechol oxidases from Lycopus europaeus and Populus nigra: evidence for a dinuclear copper center of type 3 and spectroscopic similarities to tyrosinase and hemocyanin.

We purified two catechol oxidases from Lycopus europaeus and Populus nigra which only catalyze the oxidation of catechols to quinones without hydroxylating tyrosine. The molecular mass of the Lycopus enzyme was determined to 39,800 Da and the mass of the Populus enzyme was determined to 56,050 Da. Both catechol oxidases are inhibited by thiourea, N-phenylthiourea, dithiocarbamate, and cyanide, but show different pH behavior using catechol as substrate. Atomic absorption spectrosopic analysis found 1.5 copper atoms per protein molecule. Using EPR spectroscopy we determined 1.8 Cu per molecule catechol oxidase. Furthermore, EPR spectroscopy demonstrated that catechol oxidase is a copper enzyme of type 3. The lack of an EPR signal is due to strong antiferromagnetic coupling that requires a bridging ligand between the two copper ions in the met preparation. Addition to H2O2 to both enzymes leads to oxy catechol oxidase. In the UV/Vis spectrum two new absorption bands occur at 345 nm and 580 nm. In accordance with the oxy forms of hemocyanin and tyrosinase the absorption band at 345 nm is due to an O2(2-) (pi sigma *)-->Cu(II) (dx2 - y2) charge transfer (CT) transition. The absorption band at 580 nm corresponds to the second O2(2)- (pi v*)-->Cu(II) (dx2 - y2) CT transition. The UV/Vis bands in combination with the resonance Raman spectra of oxy catechol oxidase indicate a mu-eta 2:eta 2 binding mode for dioxygen. The intense resonance Raman peak at 277 cm-1, belonging to a Cu-N (axial His) stretching mode, suggests that catechol oxidase has six terminal His ligands, as known for molluscan and arthropodan hemocyanin.

Binding Sites↗
PubMed1988

Evaluation of the cytotoxic potential of catechols and quinones structurally related to butylated hydroxyanisole.

The cytotoxicity of 2- and 3-butylated hydroxyanisole (BHA) and 18 related aromatic compounds has been determined employing cultured P388 and KB cells. The phenolic compounds, 3-BHA and 2-BHA, had moderately low cytotoxic activity. Their corresponding catechols had ED50 values that were much lower than those of the parent compounds. This substantial increase in the cytotoxic activity is attributed to the presence of the catechol group, which is known to undergo one-electron oxidation readily to give the corresponding semiquinone radical. Other related catechols had similar cytotoxic activity. In general, derivatization of the catechol functionality resulted in a decrease of the cytotoxic potential of the compounds. Monoacetylation or monomethylation of the catechols gave products that were less potent cytotoxic agents than the parent compounds. Further loss of activity was observed when both hydroxy groups of the catechol function were blocked. Substitution of a methoxy group in place of a hydrogen atom in these compounds resulted in a significant increase of cytotoxicity, whereas the replacement of a methoxy group with a methyl group reduced the cytotoxicity. The catechols and quinones derived from 2-BHA were more active when compared with those derived from 3-BHA. The t-butyl group adjacent to the catechol or quinone moiety in the 3-BHA derivatives appeared to exert a significant steric effect toward the cytotoxic potential of these compounds. These results suggest the potential use of o-quinones and catechols as cytotoxic and antitumor agents.

Butylated Hydroxyanisole↗
PubMed1997

The effects of catechol on various membrane conductances in lumbar sympathetic postganglionic neurones of the guinea-pig.

The effects of catechol on membrane properties in lumbar sympathetic postganglionic neurones isolated from guinea-pigs were studied in vitro in current and voltage clamp using single intracellular microelectrodes. Neurones with properties characteristic of two previously described classes of neurone (phasic and tonic) were studied. Catechol (3-12 mM) produced a few mV depolarization and a dose-dependent increase in membrane resistance which were both larger in tonic than in phasic neurones. In the presence of catechol, both phasic and tonic neurones fired only a single action potential at the beginning of a maintained depolarizing current step. In both neurone types, catechol reduced action potential amplitude and slowed its time course. The peak of the afterhyperpolarization became delayed and reduced in amplitude, particularly in tonic neurones. The time constant of inactivation of IA was reduced by catechol without change in the voltage sensitivity of activation or inactivation: IC50 was 3 mM in phasic and 4 mM in tonic neurones. Catechol also blocked a slow voltage-activated K+ current (resembling ID) that was present in many tonic neurones. Catechol did not modify the slow calcium-activated potassium current (gKCa1) or the anomalous rectifier; neither did it appear to affect the fast calcium-activated potassium current (IC) or the delayed rectifier. Catechol did not change the overall rate of spontaneous synaptic activity nor enhance the release of quanta of ACh from preganglionic terminals evoked by nerve stimulation. We conclude that, in addition to blocking IA, catechol blocks the slow ID-like current in sympathetic neurones. It also has a profound effect on the action potential probably by increasing inactivation of voltage-dependent Na+ channels. The change from tonic to phasic discharge in tonic neurones cannot be attributed solely to its effects on IA.

Action Potentials↗
PubMed1996

Characterisation of a chromosomally encoded catechol 1,2-dioxygenase (E.C. 1.13.11.1) from Alcaligenes eutrophus CH34.

Alcaligenes eutrophus CH34 used benzoate as a sole source of carbon and energy, degrading it through the 3-oxoadipate pathway. All the enzymes required for this degradation were shown to be encoded by chromosomal genes. Catechol 1,2-dioxygenase activity was induced by benzoate, catechol, 4-chlorocatechol, and muconate. The enzyme is most likely a homodimer, with an apparent molecular weight of 76,000 +/- 500. According to several criteria, its properties are intermediate between those of catechol 1,2-dioxygenases (CatA) and chlorocatechol 1,2-dioxygenases (ClcA). The determined Km for catechol is the lowest among known catechol and chlorocatechol dioxygenases. Similar Km values were found for para-substituted catechols, although the catalytic constants were much lower. The catechol 1,2-dioxygenase from strain CH34 is unique in its property to transform tetrachlorocatechol; however, excess substrate led to a marked reversible inhibition. Some meta- and multi-substituted catechols behaved similarly. The determined Km (or Ki) values for para- or meta-substituted catechols suggest that the presence of an electron-withdrawing substituent at one of these positions results in a higher affinity of the enzyme for the ligand. Results of studies of recognition by the enzyme of various nonmetabolised aromatic compounds are also discussed.

Alcaligenes↗
PubMed1994

Immunohistochemical study of catechol-O-methyltransferase in the human mesostriatal system.

The cellular localization of catechol-O-methyltransferase was analysed in the mesostriatal system of human brain post mortem by means of immunohistochemistry. In the human nigral complex, catechol-O-methyltransferase immunostaining was not detected in melanized dopaminergic neurons, except in the ventral tegmental area and substantia nigra pars lateralis, where few neurons displayed intense immunolabelling. In the striatum, catechol-O-methyltransferase immunostaining was found in numerous cell bodies and in the neuropile. Observations at the electron microscope level revealed that catechol-O-methyltransferase immunoreactivity was present in the cell bodies of neurons and their processes, including the dendritic spines. No catechol-O-methyltransferase immunolabelling was observed in striatal nerve terminals in contact with dendritic spines, indicating that dopaminergic nerve terminals do not exhibit catechol-O-methyltransferase immunoreactivity. Catechol-O-methyltransferase-immunoreactive cell bodies and processes of glial cells were also detected in the striatum. The data suggest that catechol-O-methyltransferase is either not expressed or only slightly expressed by the dopaminergic nigrostriatal neurons, whereas it is clearly present in striatal neurons and glial cells. Thus, the catabolic degradation of striatal released dopamine by its O-methylation may involve postsynaptic neurons rather than dopaminergic presynaptic neurons. The presence of catechol-O-methyltransferase in some dopaminergic neurons of the ventral tegmental area and substantia nigra pars lateralis suggests that methylation of dopamine may occur in these neurons, which may consequently be better protected against dopamine auto-oxidation than those of the substantia nigra pars compacta.

Animals↗
PubMed1999

Simultaneous quantitation of etoposide and its catechol metabolite in human plasma using high-performance liquid chromatography with electrochemical detection.

Etoposide, a highly active and widely used antineoplastic agent, is O-demethylated to its active catechol metabolite. A high-performance liquid chromatographic assay method for the simultaneous quantitation of etoposide and etoposide catechol in human plasma was established. Etoposide and etoposide catechol were extracted from plasma using chloroform and methanol followed by phase separation, evaporation of the organic phase, and reconstitution of the residue. Chromatography was accomplished using a reversed-phase phenyl analytical column (390 mm x 3.9 mm I.D.) with a mobile phase of 76.6% 25 mM citric acid-50 mM sodium phosphate (pH 2.4)-23.4% acetonitrile pumped isocratically at 1 ml/min with electrochemical detection. The limit of detection for etoposide was 1.2 nM and for etoposide catechol was 0.2 nM. The precision (CV) for etoposide ranged from 0.7 to 3% and for the catechol metabolite from 1 to 6%; accuracy of predicted values ranged from 97 to 106% and 94 to 103%, respectively. The assay was linear from 0.1 to 10 microM for etoposide and from 0.005 to 0.5 microM for etoposide catechol in plasma. Recovery of etoposide and etoposide catechol ranged from 93 to 95% and 90 to 98%, respectively. Stability of etoposide and etoposide catechol in human plasma containing ascorbic acid stored at -70 degrees C for one year was demonstrated. This assay procedure is suitable for evaluation of etoposide and etoposide catechol pharmacokinetics in plasma following etoposide administration.

Antineoplastic Agents, Phytogenic↗
PubMedDate not supplied

Cloning and sequence analysis of a catechol 2,3-dioxygenase gene from the nitrobenzene-degrading strain Comamonas sp JS765.

Comamonas sp strain JS765 utilizes nitrobenzene as a carbon and nitrogen source. The initial attack on nitrobenzene is carried out by nitrobenzene 1,2-dioxygenase, which converts nitrobenzene to an unstable nitrohydrodiol that spontaneously decomposes to form catechol and nitrite. Catechol is then degraded via a meta cleavage pathway. We now report the cloning of a DNA fragment carrying a catechol 2,3-dioxygenase gene from JS765. Nucleotide sequence analysis revealed three open reading frames (ORFs) predicted to encode proteins of 33.6, 13.0, and 35.0 kDa. Homology searches of the deduced amino acid sequences of three proteins suggested that ORF1 encodes a LysR-type transcriptional regulator, ORF2 encodes a XylT-type ferredoxin, and ORF3 encodes a catechol 2,3-dioxygenase. The putative regulatory gene, designated cdoR, is divergently transcribed from the ferredoxin and catechol dioxygenase genes, cdoT and cdoE, respectively. The catechol 2,3-dioxygenase is most similar in amino acid sequence to the 1.2.C subfamily of extradiol dioxygenases which include 3-methylcatechol 2,3-dioxygenase from the aniline- and toluidine-degrading Pseudomonas putida UCC2, TbuE from the toluene monooxygenase pathway of Pseudomonas pickettii PKO1 and catechol 2,3-dioxygenase II from the TOL plasmid pWW15. The substrate range of the catechol 2,3-dioxygenase produced by the recombinant E. coli strains was very similar to that of the enzyme present in nitrobenzene-grown JS765, suggesting that we have cloned the catechol 2,3-dioxygenase gene required for nitrobenzene degradation.

Amino Acid Sequence↗
PubMed1998

Catechol activation in the vasomotor center upon emergence from anesthesia: specificity.

The rostral ventrolateral medulla (RVLM) controls the vascular system. It may contribute to postoperative hypertension observed upon emergence from anesthesia. This structure contains adrenergic cardiovascular neurons. Therefore, one question was addressed: does a change in RVLM catechol activity occur upon emergence from anesthesia? Halothane-anesthetized, paralyzed rats had their ventilatory, circulatory, and acid-base stability controlled. All pressure points and incisions were infiltrated with local anesthetic. With in vivo electrochemistry, a catechol signal was recorded in the RVLM in the following circumstances: (1) under stable halothane anesthesia for 120 minutes (halothane group), (2) during 120 minutes after halothane discontinuation (saline-emergence group), (3) during 60 minutes after halothane discontinuation followed by 60 minutes after halothane readministration (readministration group), (4) emergence in rats treated with atenolol and nitroprusside to hold blood pressure as close as possible to baseline, (5) emergence after morphine 1 mg.kg(-1) i.v., (6) emergence after decerebration, and (7) emergence upon recording in the mid-brain dopaminergic A10 area. Stable halothane anesthesia (n = 6) led to no change in mean arterial pressure (MAP), heart rate (HR), and catechol signal (CAOC). During emergence from anesthesia (n = 6), MAP, HR, and catechol signal increased and did not return to baseline. By contrast, a return of MAP, HR, and catechol signal to baseline was observed upon readministration of halothane (n = 6). Whereas blood pressure and heart rate were maintained as closely as possible to baseline, a large catechol activation (n = 5) was observed upon emergence from anesthesia. A catechol activation from a lowered baseline was observed upon emergence following morphine administration (n = 5). A minor circulatory activation without RVLM catechol activation was observed upon emergence following decerebration (n = 5). Recordings in the A10 area revealed no increase in the catechol signal following emergence (n = 5). Adrenergic RVLM neurons appear to be responsive upon emergence from anesthesia, possibly being activated by suprapontine afferents impinging on the RVLM.

Adrenergic beta-Antagonists↗