Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the mechanisms responsible for chemically induced oxidative stress are under intense investigation, little is known about the effects of prooxidant chemicals on the expression of drug-metabolizing enzymes. We examined the effects of diquat (0.1 mmol/kg, ip) and ciprofibrate (0.025% w/w, diet), chemicals which induce oxidative stress via different biochemical mechanisms, on the steady-state messenger RNA (mRNA) levels of six cytochrome P450 enzymes, seven glutathione S-transferase (GST) isoenzymes, UDP-glucuronosyl transferase 1-06 (UGT1*06), gamma-glutamylcysteine synthetase (gamma GCS), NADP(H):quinone oxidoreductase (quinone reductase), Cu/Zn superoxide dismutase (SOD), catalase, and 18S ribosomal RNA in the livers of male Sprague-Dawley rats. Effects of chemical treatments on mRNA levels were compared to changes in catalytic activities for selected enzymes. Ciprofibrate treatment selectively decreased CYP1A2 mRNA expression, whereas both chemicals suppressed CYP3A2 mRNA expression. CYP4A1 mRNA expression and lauric acid hydroxylase activities were induced by ciprofibrate treatment, whereas diquat treatment moderately increased CYP4A1 mRNA levels without affecting lauric acid hydroxylase activities. The steady-state mRNA levels encoding constitutively expressed GST isozymes (Ya1, Ya2, Yb1, Yb2, and Yc1) were decreased by diquat exposure, and the mRNA encoding four of the five constitutively expressed GSTs (Ya1, Ya2, Yb1, and Yc1) were also decreased by ciprofibrate treatment. Nonconstitutively expressed or low constitutively expressed genes (CYP1A1, CYP2B1, CYP2B2, GST Yc2, GST Yf, and UGT1*06) were not induced by exposure to the prooxidants. Changes in isozyme-specific catalytic activities were more consistent with the observed changes in mRNA expression for the GSTs than for the P450s. Both treatments had inhibitory effects on hepatic GSH biosynthesis by decreasing gamma GCS large-subunit mRNA expression, gamma GCS catalytic activities, and hepatic GSH concentrations. Cu/Zn SOD and quinone reductase mRNA levels were increased after ciprofibrate exposure, whereas Cu/Zn SOD mRNA expression was decreased in the diquat-treated animals. The results of this study indicate that diquat and ciprofibrate can decrease the expression profile of a number of phase I, phase II, and antioxidant enzymes and inhibit GSH biosynthesis. These effects may involve the pretranslational loss of hepatic mRNAs, possibly due to accelerated production of reactive oxygen species.
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PMID:The effects of diquat and ciprofibrate on mRNA expression and catalytic activities of hepatic xenobiotic metabolizing and antioxidant enzymes in rat liver. 767 60

The cytotoxicity and apoptosis-inducing activity of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and 2-tert-butyl-4-methylphenol (BMP) and the mixture of BHA and BHT (BHA/BHT) (1:1, molar ratio) were investigated, using human promeylocytic leukemia cell lines (HL-60) and human squamous cell carcinoma cell lines (HSC-2). The 50% cytotoxic concentration (CC50) declined in the order of BHA, BHT (0.2-0.3 mM) > BHA/BHT (0.04-0.07 mM) > BMP (0.02-0.05 mM). The addition of antioxidants (N-acetyl-Lcysteine, sodium ascorbate, catalase) reduced the cytotoxicity of BHA/BHT or BMP against HSC-2 cells, but not that of BHA or BHT, whereas the addition of NADH, a quinone reductase to BMP, enhanced the cytotoxicity. These findings suggested that the cytotoxicity of BHA/BHT and BMP might be caused by reactive intermediates. BHA-induced cytotoxicity was enhanced by horseradish peroxidases, suggesting that BHA was oxidizable and produced cytotoxic BHA radicals. Internucleosomal DNA fragmentation of HL-60 cells was preferably induced by BHA/BHT and BMP, followed by BHA. The MnSOD mRNA expression in HL-60 cells assayed by reverse transcriptase-polymerase chain reaction was highly inhibited by BHA/BHT or BMP, accompanied by the change in the electrophoretic mobility of MnSOD on polyacryamide gel. These compounds activated caspase-3, 8 and 9 in HL-60 cells. Activations of caspases, particularly caspase-3, declined in the order of BHA/BHT > BHA > BMP > BHT. The most cytotoxic BMP activated caspase-3 activity to the least extent, possibly in part due to the occurrence of necrosis. The great cytotoxicity and apoptosis induction by BHA/BHT may be due to reactive intermediates derived from the interaction between BHA phenoxyl radical and BHT or BHT phenoxyl radical.
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PMID:Cytotoxicity and apoptosis induction by butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). 1498 15

Lawsone is an active naphthoquinone derivative isolated from henna (Lawsonia inermis L.), a widely used hair dye. Previous study on the toxicity of lawsone remains unclear since the involvement of oxidative stress and the kind of ROS (reactive oxygen species) involved have not been fully resolved yet. This present study reports the cytotoxic effects of lawsone and henna. We carried out CAT assay (a zone of inhibition test of bacterial growth and colony-forming efficiency test of transformant Escherichia coli strains that express mammalian catalase gene derived from normal catalase mice (Cs(a)) and catalase-deficient mutant mice (Cs(b))), Ames mutagenicity assay and H(2)O(2) generation assay. Lawsone generated H(2)O(2) slightly in phosphate buffer system and was not mutagenic in Ames assay using TA 98, TA 100 and TA 102, both in the absence and presence of metabolic activation. Lawsone exposure inhibited the growth of both Cs(a) and Cs(b) strains in a dose-dependent manner. Mean zone diameter for Cs(a) was 9.75+/-0.96 mm and 12.75+/-1.5 mm for Cs(b). Natural henna leaves did not show toxic effects, whereas two out of four samples of marketed henna products were shown toxicity effects. Catalase abolished zone of inhibition (ZOI) of marketed henna products, eliminated ZOI of lawsone in a dose-dependent manner and low concentration of exogenous MnSOD and Cu/ZnSOD eliminated the toxicity. Histidine and DTPA, the metal chelator; BHA and low concentration of capsaicin, the inducer of NADH-quinone reductase, effectively protected Cs(a) and Cs(b) against lawsone in this study. We suggest that lawsone cytotoxicity is probably mediated, at least in part, by the release of O(2)(-), H(2)O(2) and OH(-).
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PMID:Cytotoxicity of lawsone and cytoprotective activity of antioxidants in catalase mutant Escherichia coli. 1744 76

We have examined the role of melatonin receptor MT2 and quinone reductase II in the regulation of the redox status of preadipocytes (3T3-L1) in vitro. 3T3-L1 cells were treated with melatonin at a physiological concentration (10(-9) mol/L) and a supraphysiological (pharmacological) concentration (10(-3) mol/L) for 24 h. Luzindole (10(-4) mol/L), an antagonist of MT2 receptor, and prazosin (10(-5) mol/L), an inhibitor of quinone reductase II, were added 30 min before subsequent exposure of the cells to melatonin. The level of oxidative stress was determined by the analysis of activities of enzymes neutralising reactive oxygen species, and determination of the malondialdehyde (MDA) content. Melatonin increased activities of manganese and copper-zinc superoxide dismutase (MnSOD, Cu/ZnSOD) and catalase (CAT) at both a physiological concentration (10(-9) mol/L) and a pharmacological concentration (10(-3) mol/L). MDA content was unchanged, whereas activities of glutathione peroxidase (GSH-Px) and glutathione reductase (GSSG-Rd) were increased only by the physiological concentration. Both effects were partially inhibited by luzindole, but not prazosin. These observations suggest that melatonin, acting at least partially via MT2 receptors, can increase antioxidant enzymes activities in 3T3-L1 preadipocytes.
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PMID:Role of melatonin receptor MT(2) and quinone reductase II in the regulation of the redox status of 3T3-L1 preadipocytes in vitro. 2355 6