Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The activities of xenobiotic-metabolizing enzymes were determined in hybrid cell lines (hepatocytoma, HPCT) which have been established by fusion of liver parenchymal cells from adult rat (PC) with cells from a Reuber hepatoma cell line (FAO). 2. Cytochrome P450 was not measurable spectrophotometrically in FAO and HPCT. P450-dependent conversion of testosterone was below the detection limit in FAO and only marginally present in HPCT. 3. Microsomal and cytosolic epoxide hydrolase, glutathione S-transferase and phenol sulphotranserase were low or even below detection limit in FAO. These enzyme activities were significantly higher in HPCT and correspond to about 1-10% the activities measured in PC. 4. 1-Naphthol UPD-glucuronosyl transferase activity was about 20% in FAO and about 100% in HPCT compared to PC. 5. Metabolic conversion of benzo[a]pyrene was low in FAO, high in PC, and intermediate in HPCT. The presented data, however, do not allow the conclusion whether this intermediate rate is catalyzed by similar P450 isoenzymes as in PC. 6. Due to the easily measurable phase II-metabolizing enzyme activities HPCT may, however, be useful for in vitro enzyme induction or repression studies.
 ...
PMID:Xenobiotic-metabolizing enzyme activities in hybrid cell lines established by fusion of primary rat liver parenchymal cells with hepatoma cells. 149 90

Microsomal cytochrome P450 content, NADPH-cytochrome c reductase, and phase I (ethoxycoumarin and ethoxyresorufin O-dealkylases) and phase II (glutathione S-transferase and UDP-glucuronyltransferase) activities were studied in the liver and intestine of the striped mullet (Mullus barbatus) for 8 months (before and during sexual maturation). Biotransformation activities were much lower in extrahepatic tissues than the corresponding activities in the liver. Intestinal and hepatic biotransformation activities presented similar seasonal fluctuations: Phase I activity increased from October to February (during water cooling) and generally decreased before spawning; Phase II activity was not greatly different. Moreover, NADPH-cytochrome c reductase, ethoxyresorufin O-dealkylase, and glutathione S-transferase activities were measured in the kidney during the sexual maturation period. Renal phase I and phase II activities showed very little fluctuation during the 5 months studied. Cytochrome P450 and ethoxycoumarin and ethoxyresorufin O-dealkylases exhibited sex-linked differences during sexual maturation, whatever the tissue: in the liver the values are higher in male fish, whereas in the intestine and kidney they are lower.
 ...
PMID:Seasonal and sex-linked variations in hepatic and extrahepatic biotransformation activities in striped mullet (Mullus barbatus). 191 95

The aflatoxins are a group of closely related mycotoxins that are widely distributed in nature. The most important of the group is aflatoxin B1 (AFB1), which has a range of biological activities, including acute toxicity, teratogenicity, mutagenicity and carcinogenicity. In order for AFB1 to exert its effects, it must be converted to its reactive epoxide by the action of the mixed function mono-oxygenase enzyme systems (cytochrome P450-dependent) in the tissues (in particular, the liver) of the affected animal. This epoxide is highly reactive and can form derivatives with several cellular macromolecules, including DNA, RNA and protein. Cytochrome P450 enzymes may additionally catalyse the hydroxylation (to AFQ1 and AFM1) and demethylation (to AFP1) of the parent AFB1 molecule, resulting in products less toxic than AFB1. Conjugation of AFB1 to glutathione (mediated by glutathione S-transferase) and its subsequent excretion is regarded as an important detoxification pathway in animals. Resistance to AFB1 toxicity has been interpreted in terms of levels and activities of these detoxifying pathways. This article reviews the multiple reactions and effects attributed to aflatoxin, with particular reference to the interaction of aflatoxin with nucleic acids and proteins, and the contribution this mycotoxin has in disease development and in the promotion of hepatocellular carcinoma (HCC). The anti-mutagenic properties of several dietary factors are also considered in this article. Undoubtedly, the most important aspect of aflatoxin action is its putative role in the development of human cancer, in particular, HCC. Recently, there has been a renewed interest in this aspect and experimental evidence is rapidly accumulating at the molecular level, indicating aflatoxin as an important consideration in the aetiology of human HCC.
 ...
PMID:Cellular interactions and metabolism of aflatoxin: an update. 754 Jul 67

The cytochrome P450, epoxide hydrolase, and glutathione S-transferase enzyme families play an important part in the metabolism of many carcinogens and anti-cancer drugs. The expression of two forms of cytochrome P450 (P450 1A and P450 3A), epoxide hydrolase and of the alpha, mu, and pi forms of glutathione S-transferase in normal colon, colonic adenomas, and adenocarcinoma of the colon were studied by immunohistochemistry. This allowed the precise cellular site and distribution of each enzyme to be determined. Expression of all the xenobiotic metabolising enzymes studied was almost wholly confined to the epithelial cells, whether in normal, adenoma or carcinoma samples, except that cytochrome P450 3A was also identified in mast cells and glutathione S-transferase pi was also present in chronic inflammatory cells. Cytochrome P450 was present in only a small proportion of normal colon samples, whereas epoxide hydrolase and glutathione S-transferase mu were identified in about half, and glutathione S-transferase alpha and pi in most normal samples. By contrast all the enzyme forms studied were expressed in virtually all adenomas and in over half the carcinomas. These results suggest that cytochrome P450 1A and cytochrome P450 3A are more specific markers of colonic neoplasia than epoxide hydrolase or glutathione S-transferases alpha, mu, and pi.
 ...
PMID:Xenobiotic metabolising enzyme expression in colonic neoplasia. 840 61

We have studied the expression of different xenobiotic metabolizing enzymes in primary operable breast cancer of no special type. The expression of two forms of cytochrome P450, microsomal epoxide hydrolase, and three classes of glutathione S-transferase was investigated using immunohistochemistry. The tumours were characterized by consistent expression of microsomal epoxide hydrolase and by variable expression of the two forms of cytochrome P450 and the three types of glutathione S-transferase. Cytochrome P450 1A and cytochrome P450 3A were identified in 39 and 22 per cent of tumours, respectively. In each case, immunostaining was present only in areas of invasive carcinoma. Epoxide hydrolase was identified in 89 per cent of tumours and glutathione S-transferases pi, mu, and alpha were identified in 56, 65, and 44 per cent of tumours, respectively. Immunoreactivity for epoxide hydrolase and glutathione S-transferases was identified in both tumours and non-neoplastic breast tissue. The presence of different xenobiotic metabolizing enzymes may have a role in determining the intrinsic drug resistance of breast cancer to a variety of anti-cancer drugs, and the expression of these enzymes can readily be assessed using immunohistochemistry.
 ...
PMID:Expression of xenobiotic metabolizing enzymes in breast cancer. 849 28

Cytochrome P450 2B4 lacking amino acids 2-27, CYP2B4 (delta2-27), was mutated at position 250 and expressed in E. coli fused to glutathione S-transferase. Expression of the E250S variant (holo- plus apoenzyme) proceeded to an extent comparable with that of CYP2B4 (delta2-27), while the protein level of the E250P mutant averaged 42% that of the control pigment. Comparison of these data with the corresponding reduced CO difference spectra of the various CYP2B4 (delta2-27) forms revealed that, in the control and E250S preparations, about 90% and 44%, respectively, of the total amount of hemoprotein present existed in the form of holoenzyme, whereas the E250P derivative failed to produce a reduced carbonyl complex. Thus, replacement of the negatively charged E250 with an uncharged, polar serine residue substantially hampered assembly of CYP2B4 (delta2-27); introduction of an alpha-helix-disrupting proline completely blocked the formation of holoenzyme. These phenomena suggested that the negative charge of E250, residing in the putative G helix, underwent pairing with some positively charged group, possibly H285 located in the I helix. Deletion of the negative charge obviously perturbed the active-site geometry such as to affect both the incorporation and/or retention of the heme ligand and the spectral binding of substrates such as hexobarbital.
 ...
PMID:Amino acid residue 250 has a functional role in the assembly of rabbit liver microsomal cytochrome P450 2B4. 962 69

Antioxidant and hepatoprotective actions of the mold Monascus anka (also called Beni-Koji in Japan) against acetaminophen (AAP)-induced liver toxicity were investigated. Serum aspartate aminotransferase and glutathione S-transferase (GST) activities increased by AAP (180 mg/kg, i.p.) treatment were depressed when the Beni-Koji preparation (4 ml/kg, i.p.) was given 15 and 1 hr before AAP administration. The decrease in liver cytosolic GST activity by AAP, reflecting the release of the enzyme into serum, was also blocked by the mold. Cytochrome P450 activity was inhibited by the Beni-Koji preparation. These results suggest that M. anka prevents AAP-induced liver toxicity by both antioxidant action and the inhibition of AAP metabolism.
 ...
PMID:Protective effect of the mold Monascus anka against acetaminophen-induced liver toxicity in rats. 980 66

Indole-3-ylcarbinol (13C) is formed during processing of cruciferous vegetables and is suggested to be one of the modulators of drug-metabolising enzymes. Indole-3-ylcarbinol is a far less efficient inducer of hepatic enzymes after parenteral than after oral administration, due to formation of active metabolites in the gastrointestinal tract. As indole-3-ylcarbinol is unstable in weakly acidic aqueous solutions, non-active condensation products may be formed from indole-3-ylcarbinol, that cannot be transformed to the active products when reaching the stomach. The purpose of the present study was to test the ability of the condensation products formed at a pH corresponding to that of fresh vegetable juice to modulate the metabolism of xenobiotics. Indole-3-ylcarbinol was incubated in vitro at room temperature in the dark at pH 5.5 and samples taken at various times, for oral administration to rats and for chemical analysis. Indole-3-ylcarbinol was rapidly transformed into various oligomeric products. The 7-ethoxyresorufin O-deethylase activities (marker of cytochrome Cytochrome P450 1A enzymes, CYP1A) in liver, kidney and colon increased with the duration of the in vitro condensation period whereas the formation of 6beta-, 15beta- and and 2alpha-hydroxytestosterone was not affected significantly, indicating no effect on CYP2C11 or CYP3A enzymes. The hepatic metabolism of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). was increased by indole-3-ylcarbinol condensation products and the 4'-OH-PhIP/N-OH-PhIP ratio was decreased due to a significantly increased formation of the proximate genotoxic metabolite. N-OH-PhIP. The activities of DT-diaphorase and glutathione S-transferase were not changed significantly in the rat organs. These experiments clearly indicate that indole-3-ylcarbinol is not the definitive CYP1A inducer and that indole-3-ylcarbinol at near-neutral pH, is transformed to compounds that are inducers by themselves or may be further converted into inducing compounds in the rat stomach. Also, the enzyme inducing potency of indole-3-ylcarbinol containing vegetable juice is apparently enhanced by incubation in vitro before the intake.
 ...
PMID:Modulation of drug-metabolising enzyme expression by condensation products of indole-3-ylcarbinol, an inducer in cruciferous vegetables. 1006 48

Tumour formation may involve interactions between genetic factors and environmental carcinogens. Adenoma formation in APCMin/+ mice is associated homozygous adenomatous polyposis coli (APC) gene mutation, but the effects on carcinogen susceptibility are unknown. This study tests the hypothesis that APCMin/+ adenoma formation is accompanied by changes in metabolic proficiency and carcinogen susceptibility. Cytochrome P450 (CYP)1A1/1A2, glutathione S-transferase (GST)alpha, mu and pi classes and DNA adduct formation were assayed in adenomas and uninvolved mucosa from APCMin/+ mice, before and after benzo[a]pyrene (B[a]P) treatment. In untreated adenomas and mucosa, CYP1A1/1A2 and B[a]P-DNA adducts were undetected but GSTalpha, mu and pi class enzymes were constitutively expressed. In adenomas, B[a]P only induced CYP1A1/1A2 to low level while GSTalpha and pi class enzymes were unaffected. A GST mu band which was absent from mucosa, was induced in adenomas. In mucosa, B[a]P induced CYP1A1/1A2 and GSTalpha and pi, to high levels. B[a]P-DNA adduct levels were 56 +/- 15/10(8) nucleotides (median +/- SE) in adenomas versus 89 +/- 19/10(8) nucleotides in mucosa (P < 0.0001). APCMin adenomas show reduced bioactivation capacity and sustain less DNA damage from B[a]P exposure, than APCMin uninvolved mucosa. These properties could influence mutagenesis and subsequent neoplastic transformation of adenomas.
 ...
PMID:Metabolic proficiency and benzo[a]pyrene DNA adduct formation in APCMin mouse adenomas and uninvolved mucosa. 1035 94

The effect of 16 d intake of 300 mg carotenoids/kg diet (beta-carotene (beta C), bixin (BX), lycopene (LY), lutein (LU), canthaxanthin (CX) or astaxanthin (AX) on xenobiotic metabolizing enzymes in the liver, lung, kidney and small intestine of male Wistar rats was assessed. A control group received the basal diet (AIN-76) without carotenoids and a positive control group for enzyme induction received 3-methylcholanthrene (3-MC) at 666 mg/kg diet. Cytochrome P450 activity was assessed using the substrates ethoxyresorufin for P450 1A1, methoxyresorufin for P450 1A2, pentoxyresorufin for P450 2B1/2 and benzyloxyresorufin for P450 types 1A1/2, 2B1/2 and 3A. Glutathione-S-transferase (EC 2.5.1.18) and reduced glutathione status were assessed. Carotenoid uptake by the tissues was also determined. 3-MC and the carotenoids BX, CX and AX led to significant increases compared with control in liver, lung and kidney ethoxyresorufin-O-deethylation. Methoxyresorufin-O-demethylation activity was significantly increased in liver and lung by BX, CX and AX but only CX and AX significantly increased activity in kidney. Pentoxyresorufin-O-depentylation and benzyloxyresorufin-O-dearylation increased in liver of 3-MC-, BX-, CX- and AX-treated rats, but to a much lesser degree than for the other two substrates. Benzyloxyresorufin-O-dearylation in lung was significantly decreased by all carotenoids. Activities of any of the measured enzymes in the small intestine were undetectable in all treatment groups except the 3-MC group. Glutathione status was unaffected by any of the treatments. This is the first study identifying the carotenoids BX, CX and AX as inducers of rat lung and kidney xenobiotic metabolizing enzymes.
 ...
PMID:Effect of dietary supplementation with carotenoids on xenobiotic metabolizing enzymes in the liver, lung, kidney and small intestine of the rat. 1043 50


1 2 3 4 Next >>