Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies from our laboratories have linked the protective abilities of IH636 grape seed proanthocyanidin extract (GSPE) with inactivation of anti-apoptotic gene bcl-XL, and modification of several other critical molecular targets such as DNA-damage/DNA-repair, lipid peroxidation and intracellular Ca2+ homeostasis. Especially, GSPE provided dramatic protection against acetaminophen (APAP)-induced hepatotoxicity, significantly increased bcl-XL expression in the liver, and antagonized both necrotic and apoptotic deaths of liver cells in vivo. However, it was not clear from this study whether anti-apoptogenic and anti-necrotic effects of GSPE were: (i) due to its interference with endonuclease activity, (ii) due to its antioxidant effect, or, (iii) due to its ability to inhibit microsomal drug metabolizing enzyme(s), such as CYP-4502E1. Since CYP-4502E1 primarily metabolizes acetaminophen in mice and rats, this study specifically focused on CYP-4502E1's catalytic activity in vitro. Overall this investigation compared the in vitro aniline hydroxylation patterns of: (i) in vivo GSPE-exposed and unexposed (control) mouse liver microsomes, (ii) induced (1% acetone in drinking water for 3 days) and uninduced rat liver microsomes in the presence and absence of GSPE in vitro, and (iii) control rat liver microsomes in the presence of an anti-APAP agent 4-aminobenzamide (4-AB) in vitro. For the in vivo assessment, male B6C3F1 mice were fed GSPE diet (ADI 100 mg/kg body wt) for 4 weeks, and liver microsomes were isolated from both control and GSPE-fed mice for aniline hydroxylation, a specific marker of CYP-4502E1 activity. Data show that hydroxylation was 40% less in microsomes from GSPE-exposed livers compared to control microsomes. Similarly, when rat liver microsomes were incubated with various concentrations of GSPE in vitro (100 and 250 microg/ml), aniline hydroxylation was inhibited to various degrees (uninduced: 40 and 60% and induced: 25 and 50%, respectively with 100 and 250 microg/ml). Influence of GSPE on hydroxylation patterns were compared with another hepatoprotective agent 4-aminobenzamide (4-AB), a well-known modulator of nuclear enzyme poly(ADP-ribose) polymerase, and the data shows that 4-AB did not alter aniline hydroxylation at all. Collectively, these results may suggest that GSPE has the ability to inhibit CYP-4502E1, and this is an additional cytoprotective attribute, in conjunction with its novel antioxidant and/or antiendonucleolytic potential.
Mol Cell Biochem 2001 Feb
PMID:Differential effects of IH636 grape seed proanthocyanidin extract and a DNA repair modulator 4-aminobenzamide on liver microsomal cytochrome 4502E1-dependent aniline hydroxylation. 1133 Aug 34

Arylamine N-acetyltransferases (NATs; E.C 2.3.1.5) N-acetylate arylhydralazine and arylamine substrates using acetyl coenzyme A. Human NAT2 acetylates and inactivates the antituberculosis drug, isoniazid (INH), and is polymorphic. We previously demonstrated that there is a homologue of human NAT2 in Mycobacterium tuberculosis, whose product N-acetylates INH in vitro. We now demonstrate that the nat gene is expressed in M. tuberculosis and M. bovis Bacille Calmette-Guerin (BCG), using reverse transcription-polymerase chain reaction and Western blotting. The NAT protein is active in M. bovis BCG in vivo, as detected by the presence of N-acetyl INH in M. bovis BCG lysates grown in INH. Sequence analysis of the M. tuberculosis nat coding region reveals a single nucleotide polymorphism in 18% of a random cohort of M. tuberculosis clinical isolates, conferring a G to R change. The recombinant mutant protein appears less stable than the wild type, and has an apparent affinity for INH of 10-fold less than the wild type. Modelling the change in M. tuberculosis NAT shows that the G to R change is close to the active site, and supports the experimental findings. Minimum inhibitory concentration data suggest that this polymorphism in nat is linked to low-level changes in the INH susceptibility of M. tuberculosis clinical isolates.
Mol Microbiol 2001 Oct
PMID:Arylamine N-acetyltransferase of Mycobacterium tuberculosis is a polymorphic enzyme and a site of isoniazid metabolism. 1170 56

A set of semiempirical methods (PM3, AM1, MNDO, MNDO3, INDO, CNDO and ZINDO/1) has been tested to find the best tool for the identification of aromatic amines by infrared spectroscopy. Analysed were 1,4-, 1,3-, 1,2-phenylenediamines and aniline, amines commonly used in the dye industry. Of all the semiempirical methods tested, AM1 showed the closest correspondence to experimental values. It provided the best linearity between the calculated and experimental frequencies (correlation coefficient, cc = 0.9993). In the range of -NH2 stretching vibrations, the best correspondence between the theoretical and experimental frequencies was achieved for the PM3 method (cc = 0.8369).
Spectrochim Acta A Mol Biomol Spectrosc 2001 Nov
PMID:Semiempirical infrared spectra simulations for some aromatic amines of interest for azo dye chemistry. 1176 91

Novel chromogenic N-arylmethyl-aniline-substrates of the general formula R-NH-CH2C6H5-n-Xn (X = OH, NHR) for the localization of peroxidatic activity/hydrogen peroxide were synthesized in two steps from starting amines and aromatic aldehydes. When using 1,2-dinucleophiles (e.g. diaminobenzidine) as starting material there may be limitations resulting from dominant altemative reaction courses (amino-imines vs bis-imines) or tautomerism (amino-imines vs benzimidazolines). This has been investigated in a model study on 1,2-phenylendiamine. All substrates were evaluated for application in histochemistry, electrophoresis, colorimetry and electron microscopy. Thus, 1/ endogenous peroxidatic activity in native cryotome sections of Wistar rats was stained. One selected reagent was used for immuno-histochemical demonstration of vimentine and applied for laser microscopy at 543 nm as well. 2/ Electro-blotted dilution series of horseradish peroxidase were stained and reagents ranked according to their sensitivity. 3/ In test tube experiments precipitation behavior, color and solubility of precipitates was investigated. 4/The chromogens are capable of forming electron opaque final reaction products by way of increased osmiophilicity of the specific reaction product or/and by complexation of electron dense metals as demonstrated by electron microscopical investigations. As a result, two novel reagents derived from 1,2-phenylendiamine and 2-aminophenol are recommended especially for electron microscopy: The discrimination between internum and extemum of specific granules after osmium tetroxide treatment is resolved clearly as compared with results obtained with the standard Kamovsky protocol.
Cell Mol Biol (Noisy-le-grand) 2001
PMID:Towards versatile metal associating substrates for the determination of peroxidatic activity/hydrogen peroxide by chemical designing of Schiff base derivatives. 1193 69

The UV fluorescence excitation and dispersed fluorescence spectra of a jet-cooled o-methylaniline have been obtained for the S1 <-- S0 transition, in which some of the bands have been observed and assigned for the first time. The origin of the electronic transition appears at 34,328.4 cm(-1). It was found that the spectra exhibit an important feature corresponding to the internal rotation of the methyl group in the electronic ground and excited states. Ab initio calculations at MP2/6-31 + G* and CIS/6-31 + G* show that the optimised structure of o-methylaniline in the ground state is not planar with the amino group having sp3 hybridation-like character due to the existence of lone paired electrons on the N atom. Upon electronic excitation, the C-N bond exhibits a partial double character, as in the case of other aniline derivatives.
Spectrochim Acta A Mol Biomol Spectrosc 2002 Mar 15
PMID:A reinvestigation of the molecular structures, vibrations and rotation of methyl group in o-methylaniline in S0 and S1 states studied by laser induced fluorescence spectroscopy and ab initio calculations. 1194 93

Arylamine N-acetyltransferases which acetylate and inactivate isoniazid, an anti-tubercular drug, are found in mycobacteria including Mycobacterium smegmatis and Mycobacterium tuberculosis. We have solved the structure of arylamine N-acetyltransferase from M. smegmatis at a resolution of 1.7 A as a model for the highly homologous NAT from M. tuberculosis. The fold closely resembles that of NAT from Salmonella typhimurium, with a common catalytic triad and domain structure that is similar to certain cysteine proteases. The detailed geometry of the catalytic triad is typical of enzymes which use primary alcohols or thiols as activated nucleophiles. Thermal mobility and structural variations identify parts of NAT which might undergo conformational changes during catalysis. Sequence conservation among eubacterial NATs is restricted to structural residues of the protein core, as well as the active site and a hinge that connects the first two domains of the NAT structure. The structure of M. smegmatis NAT provides a template for modelling the structure of the M. tuberculosis enzyme and for structure-based ligand design as an approach to designing anti-TB drugs.
J Mol Biol 2002 May 10
PMID:The structure of arylamine N-acetyltransferase from Mycobacterium smegmatis--an enzyme which inactivates the anti-tubercular drug, isoniazid. 1205 3

The hydrogen bonding of 23 aniline's derivatives in various solvents and in solid states are studied by Fourier transform infrared spectroscopy. The Infrared absorption of their amino group is greatly influenced by solvents. Compared with those data determined in hexane, the symmetric stretching frequency (nu(s)) and asymmetric stretching frequency (nu(as)) of amino group have an obvious bathochromic shift in benzene, but a relatively smaller shift in CCl4. It is also found that the concentration of these compounds has very little effect on the frequencies, the band shapes and relative absorption intensities of amino group. This indicates that the intermolecular hydrogen bonds are very weak between the aniline's derivatives in the solution. The substituent of methyl (-CH3) has different electronic effects in organic solvents with various polarities. Methyl group behaves as an electron-donating functional group in hexane, however, it shows an electron-withdrawing effect in benzene. When methoxyl (CH3O-) is ortho-substituted, v(as) of amino group increases and nu(s) almost does not change. While methoxyl (CH3O-) is meta-substituted, v(as) of amino group increases, but nu(s) decreases. The groups of chloro- (Cl-) and nitro- (-NO2) cause a hyposochromic shift of the nu(as) and nu(s) of amino group, while substituent of -NH2 makes a bathochromic shift. The solvents influence the relative intensities of nu(as) and nu(s) of amino group more greatly than the substituents do. In solid states, the amino group of aniline's derivatives has more than two absorption bands because of forming the inter- or intra-molecular hydrogen bonds.
Spectrochim Acta A Mol Biomol Spectrosc 2002 Nov
PMID:Studies on the hydrogen bonding of aniline's derivatives by FT-IR. 1247 25

Biochemical measurements in the sentinel clam Chamaelea gallina have been used as biomarkers of marine pollution. In this study, S9, cytosolic fractions (CF), and microsomal fractions (MF) prepared from unexposed clams and clams exposed to model pollutants were used to activate 2-aminoanthracene (2-AA) and 2-acetylaminofluorene (AAF) to mutagens in Salmonella typhimurium strain BA149, which overexpresses O-acetyltransferase. Arylamine activation was similar with subcellular fractions from unexposed and Aroclor 1254-exposed clams, but decreased with fractions from As(III)- and Cu(II)-exposed clams. Bioactivation of arylamines by CF was higher than by MF, and higher with NADH than with NADPH as the reducing agent. alpha-Naphthoflavone inhibited AAF activation by CF and MF, but increased 2-AA activation nearly twofold. In contrast to the results with arylamine activation, benzo[a]pyrene hydroxylase (BPH) activity increased twofold in fractions from Aroclor 1254- and Cu(II)-exposed clams. Activation of 2-AA was also evaluated using S9 fractions from clams sampled at littoral sites with different pollutant levels. Compared to a reference site, lower 2-AA bioactivation and higher BPH activity were found in clams containing high levels of copper and organic contaminants, although the differences were not statistically significant. While these findings agree with the results of the model Cu(II) exposure, the effects of other pollutants cannot be ruled out. The results of the study demonstrate that arylamine activation by clams is not preferentially catalyzed by microsomal monooxygenases but by unknown cytosolic system(s), and that bioactivation of 2-AA and AAF appears to occur by different pathways.
Environ Mol Mutagen 2003
PMID:Mutagenic activation of arylamines by subcellular fractions of Chamaelea gallina clams exposed to environmental pollutants. 1255 92

Overtone spectra of aniline and its o-and m- chloro-derivatives mixed with carbon tetrachloride have been studied at different dilutions. Vibrational frequency and anharmonicity constants for the C-H stretch vibration and for the symmetric and asymmetric N-H stretch vibrations have been determined. The presence of intermolecular hydrogen bonding has been noted in all the three molecules. Intramolecular hydrogen bonding involving N-H...Cl has also been detected in o-chloroaniline.
Spectrochim Acta A Mol Biomol Spectrosc 2003 Apr
PMID:Overtone bands in aniline and its chloro-derivatives--a low concentration study. 1265 99

UV-visible spectroelectrochemical studies on copolymerization of diphenylamine (DPA) with ortho-methoxy aniline (OMA) were carried out for different feed ratios of DPA and OMA using indium tin oxide (ITO)-coated glass as working electrode. The UV-visible spectra show clear dependencies on the molar feed composition of DPA or OMA used in electropolymerization. Derivative cyclic voltabsorptogram (DCVA) was deduced at the wavelengths corresponding to the absorption by the intermediate species and used to confirm the intermediates generated during the electropolymerization. The composition of DPA and OMA in the copolymer for the copolymers synthesized with different molar feed ratios of DPA and OMA was determined by UV-visible spectroscopy. Reactivity ratios of DPA and OMA were deduced by using Fineman-Ross and Kelen-Tudos methods and correlated with spectroelectrochemical results.
Spectrochim Acta A Mol Biomol Spectrosc 2003 May
PMID:In situ UV-visible spectroelectrochemical studies on the copolymerization of diphenylamine with ortho-methoxy aniline. 1271 67


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