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:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunogold studies of normal human kidney and common human kidney cancers were performed using polyclonal antibodies to antioxidant enzymes, including antibodies to copper, zinc and manganese superoxide dismutases, catalase, glutathione peroxidase, and glutathione S-transferases and their subunits. Normal tissue adjacent to human renal tumors had the same antioxidant enzyme immunoreactive protein profiles as normal human kidney, thus establishing that the presence of tumor does not alter the levels of antioxidant enzyme immunoreactive proteins in adjacent kidney tissue. Levels of immunoreactive protein for antioxidant enzymes were determined in four common types of malignant renal cancer. In general, tumors had low levels of antioxidant enzymes; however, certain histologic types of renal tumors had high levels of immunoreactive protein for glutathione S-transferase subunits, which could affect their susceptibility to chemotherapy. Studies of transitional carcinoma of the renal pelvis were especially informative since it was possible to compare levels of antioxidant enzyme immunoreactive protein with adjacent normal transitional epithelium; the majority of antibodies resulted in lower levels of immunoreactive protein in transitional cell carcinoma than in adjacent normal transitional epithelium. Our results are discussed in relation to the response of renal tumors to therapy.
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PMID:Immunogold analysis of antioxidant enzymes in common renal cancers. 872 Apr 59

Cross-resistance presents an obstacle in cancer chemotherapy. Cadmium is a potential carcinogen whose exposure has been shown in epidemiological and laboratory experiments to cause lung cancer. Cadmium also induces various forms of resistance in human lung carcinoma cells. This resistance may be shared by antineoplastic agents, which should be a concern for chemotherapy of cadmium-induced lung cancer. In the present study, two subpopulations of human lung carcinoma A549 cells with a different magnitude of resistance to cadmium toxicity were shown to have a parallel resistance to the cytotoxic action of Adriamycin (ADR), an important anticancer drug. Several factors were examined to investigate the mechanism(s) for the cross-resistance, including cellular metallothionein and glutathione (GSH) concentrations, glutathione S-transferase activity, mdr1 expression, and antioxidant enzyme activities including superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Only cellular GSH content was elevated consistently in the cadmium/ADR-resistant cells relative to the cadmium/ADR-sensitive cells. Treatment with buthionine sulfoximine, a specific inhibitor of GSH synthesis sensitized both cell lines to ADR only when the cellular GSH levels were depleted to about 5% of control. This BSO treatment, however, did not affect cell viability. Further study revealed that the cadmium/ADR-resistant cells have a greater capacity in recovery of cellular GSH content following BSO treatment. The results demonstrate that cross-resistance to ADR exists in cadmium-resistant human lung carcinoma A549 cells, and enhanced GSH synthesis capacity, rather than elevated levels of cellular GSH, may be related to this resistance.
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PMID:Decreased sensitivity to adriamycin in cadmium-resistant human lung carcinoma A549 cells. 911 95

Understanding the fundamental mechanism of apoptosis is crucial to developing therapeutic strategies for controlling apoptosis in diseased tissues. We are using model systems with relevance to cancer treatment to investigate the mechanism of apoptosis. Subtraction hybridization cloning was used to identify transcripts present at higher levels in regressing vs. normal prostate; these may be important for apoptosis. One of the genes cloned from regressing prostate is also upregulated in the murine W7.2 lymphocyte cell line induced to undergo apoptosis by treatment with the synthetic glucocorticoid, dexamethasone. This gene encodes a mu class glutathione S-transferase (EC 2.5.1.18), a protein that can protect the cell against oxidative stress by repairing oxidized lipids, proteins, and DNA. Glutathione S-transferase expression does not increase with dexamethasone treatment of lymphocyte cell lines expressing nonfunctional glucocorticoid receptors or a mutation in the apoptotic pathway. Other antioxidant defenses, including catalase (EC 1.11.1.6) and superoxide dismutase (EC 1.15.1.1), decline following dexamethasone treatment of W7.2 cells. Overexpression of the bcl-2 oncogene protects these cells against dexamethasone-mediated apoptosis and prevents the decrease in antioxidant enzyme activity. These findings support the hypothesis that control of the cellular redox state is important to the mechanism of glucocorticoid-mediated lymphocyte apoptosis. Another model system we are using is tumor necrosis factor-alpha treatment of MCF-7 human breast cancer cells. Our preliminary results suggest that, in this system, activation of nuclear factor-kappa B and increased expression of manganese superoxide dismutase may afford protection from apoptosis.
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PMID:Modulation of antioxidant defenses during apoptosis. 940 33

It has been suggested that high iron stores enhance colon carcinogenesis. The effect of high dietary iron (Fe) on indices of iron, copper (Cu) and manganese (Mn) status, lipid peroxidation using the thiobarbituric acid reactive substances assay, superoxide dismutase, glutathione peroxidase, glutathione transferase and ceruloplasmin activities, cell proliferation and development of preneoplastic lesions known as aberrant crypt foci (ACF) in rat colon was examined using a 3 x 2 factorial design. Male weanling Sprague-Dawley rats were fed adequate (AFe; 45 mg Fe/kg diet), moderately high (MHFe; 225 mg Fe/kg diet) and high (HFe; 450 mg Fe/kg diet) dietary Fe for 2.5 wk, then treated with azoxymethane (AOM; 2 injections, 1 wk apart; total dose 30 mg/kg body weight) or saline (n = 14-15 per group). Dietary treatment continued for another 6 wk after the second AOM dose. At the time of AOM injection, colon Fe concentrations were one- and threefold higher for MHFe and HFe rats, respectively, than for AFe rats. It was proposed that high dietary Fe would adversely affect Cu and Mn status, resulting in impaired antioxidant enzyme activity. However, neither indices of Cu and Mn status nor colonic mucosal antioxidant enzyme activities were affected by dietary Fe except for plasma ceruloplasmin activity, which was slightly lower in rats fed high iron diets than in rats fed adequate iron diets (P < 0.01). Dietary Fe had no significant effect on colonic mucosal lipid peroxidation, cell proliferation or ACF development. In conclusion, our findings suggest that dietary Fe concentrations that are approximately 5 and 10 times adequate do not enhance oxidative stress, cell proliferation and ACF development in the colon of rats.
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PMID:Iron supplementation does not affect cell proliferation or aberrant crypt foci development in the colon of sprague-dawley rats. 952 41

Antioxidant enzyme activities were measured following exposure to hypericin +/- irradiation in EMT6 cells. CuZnSOD and catalase activities peaked within 0.5 h following irradiation for nontoxic 0.5 microM hypericin and toxic 1.0 microM hypericin. Catalase remained elevated up to 3 h for 1.0 microM hypericin + light. MnSOD activity was elevated immediately following irradiation for both doses. These levels returned to control by 1 h for 0.5 microM hypericin, but were depressed after 1 h for 1.0 microM hypericin. This suggests that mitochondria impairment may be a critical factor in hypericin phototoxicity. Glutathione reductase was inhibited immediately following irradiation with 1.0 microM hypericin, suggesting that an altered status of the glutathione pool contributed to cytotoxicity. Glutathione peroxidase activities were elevated following irradiation but returned to control levels within 0.5 h for both doses, implicating hydroperoxide formation as an early event in hypericin phototoxicity. Inhibition by hypericin in the dark was demonstrated for purified CuZnSOD, Se-dependent glutathione peroxidase, glutathione S-transferase, and glutathione reductase activities in vitro. Irradiation did not potentiate hypericin-mediated glutathione reductase inhibition and decrease inhibition for the other enzymes. Collectively, these data demonstrate an antioxidant enzyme response to hypericin photoactivation and confirm a role for oxygen in hypericin phototoxicity.
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PMID:Antioxidant enzyme response to hypericin in EMT6 mouse mammary carcinoma cells. 958 12

Dopamine (DA) is oxidized to the neurotoxic prooxidant species H2O2, OH., and DA quinones. We tested whether dimethyl fumarate (DMF), an electrophile shown to induce a pleiotropic antioxidant response in nonneuronal cells, could reduce the toxicity of DA metabolites in neural cells. Treatment of the N18-RE-105 neuroblastoma-retina hybridoma cell line with 30-150 microM dopamine led to cell death within 24 h, which increased steeply with dose, decreased with higher plating density, and was blocked by the H2O2-metabolizing enzyme catalase. Pretreatment with DMF (30 microM, 24 h) significantly attenuated DA and H2O2 toxicity (40-60%) but not that caused by the calcium ionophore ionomycin. DMF treatment also elevated total intracellular GSH and increased activities of the antioxidant enzymes quinone reductase (QR), glutathione S-transferase (GST), glutathione reductase, and the pentose phosphate enzyme glucose-6-phosphate dehydrogenase. To assess the protective efficacy of QR and GST, a stable cell line was constructed in which these enzymes were overexpressed. Cell death in the overexpressing line was not significantly different from that in a cell line expressing normal QR and GST activities, indicating that these two enzymes alone are insufficient for protection against DA toxicity. Although the relative importance of a single antioxidant enzyme such as QR or GST may be small, antioxidant inducers such as DMF may prove valuable as agents that elicit a broad-spectrum neuroprotective response.
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PMID:Activation of endogenous antioxidant defenses in neuronal cells prevents free radical-mediated damage. 964 52

The current experiments were designed to study the effect of dietary n-6 and n-3 polyunsaturated fatty acids on antioxidant enzyme activity and dexamethasone (DEX)-induced apoptosis in spleen cells of sedentary (Sed) and treadmill-exercised (Ex) ICR male mice. Two-month-old mice maintained on AIN 76 formula diet, supplemented with either 5% corn oil (CO) or 5% fish oil (FO) diets, were trained on a treadmill to run from 45 to 50 min 1 km/day, 6 days a week for 12 weeks. After 12 weeks of exercise, both Sed and Ex groups were sacrificed. Blood and various tissues, including spleen, were collected asceptically. Increased serum and spleen homogenate peroxide [malondialdehyde (MDA)] levels were observed in mice fed FO (n-3 PUFA) diets, compared to mice fed CO (n-6 PUFA). However, exercise did not alter MDA levels in either CO- or FO-fed mice. Feeding n-3 PUFA significantly increased superoxide dismutase (SOD), catalase, and glutathione peroxidase activity of spleen homogenates. Exercise also significantly increased SOD and peroxidase in CO-fed animals, whereas catalase, glutathione peroxidase, and glutathione transferase were higher in FO-fed mice, compared to the Sed group. Apoptosis and necrosis were quantitated in splenocytes incubated with or without 1 microM Dex in RPMI medium for 8 and 24 hr. Cells were stained with Annexin V and propidium iodide (PI) for apoptotic and necrotic cells. FO-fed mice showed higher apoptosis (64 vs 50%) and necrosis (40 vs 22%) in spleen cells than CO-fed mice. Cells from FO-fed mice, incubated in medium alone, showed increased apoptosis (112%) 24 hr after incubation, and necrosis (37 and 70%) at 8 and 24 hr of incubation, compared to CO-fed mice. In Ex group, apoptosis was increased in both CO- and FO-fed mice only at 24 hr after incubation. In summary, these results indicate that FO (n-3 PUFA-enriched) diets increase apoptosis and antioxidant enzyme activity in spleen cells, probably due to elevated lipid peroxides.
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PMID:Modulation of antioxidant enzymes and apoptosis in mice by dietary lipids and treadmill exercise. 1008 Jan 3

The activities of antioxidant enzymes, and the expression of p21(WAF1) and p53 proteins were studied at different times after subculture during proliferation and differentiation phases. Two human melanoma cell lines were used: IPC182, which is a non-differentiating cell line, and IGR221, which spontaneously differentiates at the end of the exponential growth phase, as evidenced by a marked increase of melanin content and tyrosinase activity. In the two cell lines, the slowing of proliferation coincided with an increase in the activity and amount of immunoreactive superoxide dismutases (SOD1 and SOD2), and a decrease of catalase and glutathione peroxidase activities, and of the glutathione content. The levels of p21WAF1 and p53 proteins were found to be lower in confluent than in proliferative cells. Several parameters were modified only during the differentiation phase of IGR221 cells; in these cells the increase of tyrosinase activity was highly correlated with the increase in SOD2, GST, glutathione reductase, and G6PD activities. The level of glutathione was found to be lower in differentiated IGR221 than in non-differentiated IPC182 cells. These results suggest that p21WAF1 and p53 proteins are not involved in the spontaneous differentiation process of melanoma cells, and that abnormal regulation of the cell cycle inhibition pathway occurred in these cells. The results sustain the hypothesis that alterations of antioxidant enzyme expression are involved in the control of proliferation and differentiation of melanoma cells. Alterations of SOD2 activity may be of particular importance, since variations are observed with both cell growth and cell differentiation.
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PMID:Modulation of antioxidant enzymes p21WAF1 and p53 expression during proliferation and differentiation of human melanoma cell lines. 1023 48

An investigation was made of ethoxyresorufin O-deethylase (EROD) activity, a cytochrome P450 (CYP) dependent enzyme mainly catalyzed by CYP1A1, glutathione S-transferase (GST) activity toward the substrates 1-chloro-2,4- dinitrobenzene (CDNB) and ethacrynic acid (EAA), reduced glutathione (GSH) levels, and antioxidant enzyme (AOE) activity namely catalase (CAT) and selenium- dependent glutathione peroxidase (Se-GPx) in tumor and surrounding tumor-free (normal) tissues in female breast cancer patients. Wide interindividual variations were found in the enzyme activities in both tumor and normal breast tissues. No significant differences were noted between mean EROD and CAT activities in tumor and normal breast tissues. The mean activities of CDNB GST, EAA GST and Se-GPx and GSH levels in tumor tissue were significantly higher than those in normal breast tissue. These results show that CYP, GST and AOE behave differentially in breast tumors.
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PMID:Xenobiotic metabolizing and antioxidant enzymes in normal and neoplastic human breast tissue. 1032 33

Comparative studies were performed on the antioxidant enzyme activities and thiobarbituric acid reactive substance (TBARS) concentration in liver and red cells of two groups of rainbow trout (Oncorhynchus mykiss). The fish of the first group were cultured in freshwater and the others were adapted to sea-water by by being transferred from freshwater at 5-6 months of age. Catalase (CAT), glutathione peroxidase (GPX), and glutathione S-transferase (GST) activities were significantly higher in hepatic and extrahepatic tissues in both of the fish groups. Superoxide dismutase (SOD) activities were found lower in the seawater-adapted trout than in the freshwater-cultured trout. In both tissues, TBARS were found significantly higher in the seawater-adapted trout than in the freshwater trout. It was also observed that the red cells of the seawater-adapted trout were much more resistant to oxidative stress than the red cells of the freshwater-cultured trout. The results implicate that antioxidant capacities in the seawater-adapted trout and freshwater trout may be related to physical and chemical characteristics of the environment.
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PMID:A comparative study of antioxidant enzyme activities in freshwater and seawater-adapted rainbow trout. 1048 21


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