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)

We have characterized a new selenium-dependent glutathione peroxidase, GSHPx-GI, by expressing a GSHPx-GI cDNA isolated from human hepatoma HepG2 cells in human mammary carcinoma MCF-7 cells, which have virtually undetectable expression of either the classical cellular enzyme, GSHPx-1, or GSHPx-GI at the protein level. One of the G418-resistant clones, neo-D1, expresses the transfected GSHPx-GI cDNA. This is based on 1) the presence of an additional GSHPx-GI DNA restriction fragment detected by Southern analysis; 2) the presence of a 1.9-kilobase (kb) GSHPx-GI mRNA in addition to the 1.0-kb endogenous mRNA by Northern analysis; and 3) the appearance of a 22-kDa 75Se-labeled protein which is absent in parental MCF-7 cells revealed by SDS-polyacrylamide gel electrophoresis. GSHPx-GI expressed in neo-D1 is a tetrameric protein localized in cytosol. GSHPx-GI does not cross-react with antisera against human GSHPx-1 or human plasma glutathione peroxidase (GSHPx-P). Similar substrate specificities are found for GSHPx-1 and GSHPx-GI; they both catalyze the reduction of H2O2, tert-butyl hydroperoxide, cumene hydroperoxide, and linoleic acid hydroperoxide with glutathione, but not of phosphatidylcholine hydroperoxide. GSHPx-GI mRNA was readily detected in human liver and colon, and occasionally in human breast samples, but not other human tissues including kidney, heart, lung, placenta, or uterus. In rodent tissues, GSHPx-GI mRNA is only detected in the gastrointestinal tract, and not in other tissues including liver. In fact, GSHPx-GI appears to be the major glutathione-dependent peroxidase activity in rodent GI tract. This finding suggests that GSHPx-GI could play a major role in protecting mammals from the toxicity of ingested lipid hydroperoxides. In conclusion, we have demonstrated that GSHPx-GI is the fourth member in the selenium-dependent glutathione peroxidase family, in addition to GSHPx-1, GSHPx-P, and phospholipid hydroperoxide glutathione peroxidase (PHGPX).
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PMID:Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI. 842 33

Oxidoreductases such as glutaredoxin are a major class of enzymes that reversibly catalyze thiol-disulfide exchange reactions. Transfection experiments using geneticin (G418) selection to identify the specific protein S-thiolated substrates of glutaredoxin-1 (Grx-1) noted the curious phenomenon that nontransfected control cells treated with G418 had increased levels of Grx-1 expression. Varied concentrations of gentamicin, kanamycin, and hygromycin increased Grx-1 expression in a time- and dose-dependent fashion in human cultured retinal pigment epithelial cells. Reactive oxygen species formation after aminoglycoside exposure correlated directly to aminoglycoside treatment. Further indication that oxidation regulates Grx-1 expression was noted by the positive effect of phorbol 12-myristate 13-acetate, a known inducer of redox-sensitive AP-1 transcription factor. In agreement with this hypothesis was the finding that the physiologic reductant N-acetylcysteine decreased Grx-1 expression whereas tert-butyl hydroperoxide increased Grx-1 expression. Our data suggest that aminoglycosides increased Grx-1 expression in response to oxidative stress.
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PMID:Endogenous oxidoreductase expression is induced by aminoglycosides. 1274 50