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)

Cu/Zn-superoxide dismutase (Cu/Zn-SOD) has been shown to modulate the autoxidation of a variety of phenoic compounds, including 1,4-hydroquinone (HQ), a benzene-derived metabolite. The acceleration of autoxidation of HQ by Cu/Zn-SOD results in the production of 1,4-benzoquinone (BQ). It has been proposed that the chemical mechanism involved in the Cu/Zn-SOD-catalyzed autoxidation of HQ may be occur through either its conventional activity as a superoxide:superoxide oxidoreductase or as a semiquinone:superoxide oxidoreductase. However, Cu/Zn-SOD-accelerated oxidation of HQ has not been resolved experimentally. In this study, with ESR spectroscopy we investigated further the chemical reactions involved in the SOD-accelerated oxidation of HQ. In phosphate-buffered saline (PSB), HQ underwent a slow autoxidation to BQ, which was accelerated by Cu/Zn-SOD, Mn-SOD, or Fe-SOD with similar efficiency. In contrast, among free metals, only Cu(II) strongly mediated the oxidation of HQ to BQ. Mn(II) exhibited a slight capacity to oxidize HQ, whereas neither FE(II) nor FE(III) was capable of modulating the autoxidation of HG. The presence of either form of SOD also dramatically enhanced the formation of semiquinone anion radicals SQ-. from HQ. The SOD-accelerated oxidation of HQ was also accompanied by the generation of H202. In PBS containing bovine serum albumin (BSA) (PBS/BSA), HQ did not undergo autoxidation to SQ-., and as such the presence of SOD was unable to induce the formation of either SQ-. or BQ or the consumption of O2. The addition of 10 microM BQ to HQ (100 or 1000 microM) in PBS/BSA resulted in the formation of SQ-. and initiated a slow rate of oxidation of HQ to BQ. In this case, the presence of Cu/Zn-SOD strongly accelerated the oxidation of HQ to SQ-. and BQ and the utilization of O2. Furthermore, the enhancement by Cu/Zn-SOD of the generation of SQ-. or BQ from HQ in PBS/BSA was extensively inhibited under anaerobic conditions. The enhancement of SQ-. generation from HQ by all three forms of SOD does not support the possibility that Cu/Zn-SOD can oxidize SQ-. to BQ. Taken together, this study demonstrates that unlike free copper, Cu/Zn-SOD does not directly interact with HQ to cause its oxidation to BQ. Rather, the autoxidation of HQ to SQ-. is a prerequisite for the enhancing capacity of Cu/Zn-SOD, and the dismutation of superoxide anion radicals generated from the SQ-. in the presence of O2 appears to be the underlying mechanism responsible for the enhancement by Cu/Zn-SOD of the oxidation of HQ.
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PMID:Role of Cu/Zn-superoxide dismutase in xenobiotic activation. I. Chemical reactions involved in the Cu/Zn-superoxide dismutase-accelerated oxidation of the benzene metabolite 1,4-hydroquinone. 864 79

Organisms exposed to ionizing radiation are mainly damaged by free radicals, which are generated by the radiolysis of water contained in the cells. Recently a significant reduction of tissue injury from irradiation damage was demonstrated by using MnSOD-plasmid/liposome treatments in the protection of murine lung. In this study we show that a new active recombinant human MnSOD (rMnSOD), easily administered in vivo, not only exerts the same radioprotective effect on normal cells and organisms as any MnSOD, but it is also radiosensitizing for tumor cells. In addition, we show how healthy animals, exposed to lethal doses of ionizing radiation and daily injections with rMnSOD, were protected from radiodamage and were still alive 30 days after the irradiation, while animals treated with only PBS solution, in the absence of rMnSOD, died after 7-8 days from the radiotreatments. The molecular analysis of all irradiated tissues revealed that the antiapoptotic AVEN gene appeared activated only in the animals treated in the presence of rMnSOD. The data suggest that rMnSOD deserves to be considered as a pharmaceutical tool for making radiotherapy more selective on cancer cells and to prevent and/or cure the accidental damage derived from exposure to ionizing radiation.
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PMID:A recombinant MnSOD is radioprotective for normal cells and radiosensitizing for tumor cells. 1899 83

The combined effect of tumor necrosis factor alpha (TNF) and adriamycin (ADR) on tumor cell killing was investigated in vivo. The human breast adenocarcinoma ADR-resistant MDA/ADR cells found to be resistant to in vitro TNF lysis and with an apparent index of resistance to ADR of 23 have been used. Treatment of MDA/ADR subcutaneous tumor bearing mice with PBS, TNF, ADR or the combination of TNF/ADR indicate that the combination of TNF and ADR treatment leads to a significant decrease in tumor growth while treatment with TNF was inactive and treatment with ADR was moderately active. Tumor cells were collected from mice treated with TNF/ADR combination and analysed by PCR for MnSOD and TNF ne expression. No induction of the expression of these genes, known to be involved in the regulation of TNF-induced cell killing, was noted following TNF/ADR combination treatment, suggesting that their products were not involved in the observed resistance.
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PMID:In-vivo effect of the combination of tnf and adriamycin against a human breast cell-line expressing the mdr-phenotype. 2155 33