Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT01586 (G418)
 2,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transfection of murine NIH3T3 fibroblasts and human MCF7 breast carcinoma cells with a pSV2-derived eukaryotic expression vector for human cytosolic glutathione peroxidase resulted in clones with increased glutathione peroxidase activity. This heterologous expression indicates that murine cells recognize the human "selenocysteine insertion sequence" in the 3' untranslated region of the mRNA which facilitates insertion of selenocysteine directed by the opal codon. Though most clones from both cell lines eventually lost their enhanced glutathione peroxidase activity despite continuous selection on G418, some NIH3T3 clones retained enhanced enzyme activity without continuous G418 exposure. Transfection of MCF7 cells with an Epstein-Barr virus (EBV)-derived episomally replicating expression vector carrying the glutathione peroxidase gene also revealed increased glutathione peroxidase activity. These MCF7 cells, however, all required exposure to G418 to maintain enhanced glutathione peroxidase activity. Detailed biochemical analysis of a stably expressing NIH3T3 clone and MCF7 expressing cells revealed no alterations in activities of copper-zinc superoxide dismutase, manganese superoxide dismutase, catalase, phospholipid-glutathione peroxidase, glutathione reductase, glutathione transferase, or NADPH-P450 reductase. Both pSV2- and EBV-derived glutathione peroxidase-expressing clones exhibited enhanced resistance to paraquat as well as to peroxides.
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PMID:Heterologous expression of selenium-dependent glutathione peroxidase affords cellular resistance to paraquat. 748 71

Overexpression of manganese superoxide dismutase (MnSOD) has been postulated as one possible mechanism of radioprotection for hematopoietic cells. In this study retroviral constructs having the human MnSOD gene in both the sense and antisense orientations and the Neo-R gene as a selectable marker were transfected into the human erythroleukemic cell line K562 and the human melanoma cell line A375 by electroporation. Stably transfected K562 and A375 cells selected in G418 for 3 weeks were subjected to various doses of irradiation, and cell viability was assayed using a colony assay system in semisolid medium. Results demonstrated that K562 cells transfected with MnSOD in the antisense orientation displayed increased sensitivity to irradiation compared to parental or vector-transfected K562 cells. In contrast, A375 cells transfected with the sense MnSOD gene demonstrated increased resistance to irradiation compared to parental or vector-transfected A375 cells. The expression of the MnSOD gene in these transfected cell lines correlates with the up- or down-modulation of radiosensitivity. Thus, increased MnSOD protein was seen in the A375 cells containing the sense MnSOD, whereas decreased MnSOD protein was seen in the K562 cells containing the antisense MnSOD. These data provide evidence for the direct role of MnSOD in radioprotection using antisense gene transfer/inhibition studies.
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PMID:Role of manganese superoxide dismutase in radioprotection using gene transfer studies. 762 Dec 45