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dc.contributor.advisorPowis, Garthen_US
dc.contributor.authorBaker, Amanda Fern, 1969-
dc.creatorBaker, Amanda Fern, 1969-en_US
dc.date.accessioned2013-04-18T09:47:44Z
dc.date.available2013-04-18T09:47:44Z
dc.date.issued1997en_US
dc.identifier.urihttp://hdl.handle.net/10150/282473
dc.description.abstractThe modulation of the antioxidant defense during dexamethasone-induced apoptosis in WEHI7.2 cells mouse lymphoid cells was studied. When treated with dexamethasone, antioxidant defense transcripts including catalase, MnSOD, CuZnSOD, DT-diaphorase, GPX, and thioredoxin exhibited a progressive decrease over 24 hours (h) in apoptosis-sensitive wild-type WEHI7.2 and apoptosis-resistant bcl-2 transfected (W.Hb12) cells. Catalase activity was maintained and total SOD and DT-diaphorase activity showed smaller decreases following dexamethasone treatment of bcl-2 transfected cells. Treatment of wild-type and bcl-2 transfected WEHI7.2 cells with a catalase inhibitor, amino-triazole, was not sufficient to induce apoptosis. Antioxidants, including bovine liver catalase, bovine erythrocyte CuZnSOD, sodium selenite and Trolox, a water soluble vitamin E analogue, as well as hypoxia, inhibited dexamethasone-induced apoptosis. Transfection of the WEHI7.2 cells with catalase and thioredoxin resulted in a significant level of protection against dexamethasone-induced apoptosis. Thioredoxin-transfected cells were also protected from apoptosis induced by staurosporine, N-acetyl-sphingosine, etoposide and thapsigargin. When inoculated into severe combined immunodeficient (scid) mice the trx transfected cells formed tumors that showed increased growth compared to wild-type as well as bcl-2 transfected WEHI7.2 cells. The trx and bcl-2 transfected cell tumors both showed less spontaneous apoptosis than tumors formed by the wild-type cells. Unlike tumors formed by the wild-type and bcl-2 transfected WEHI7.2 cells, trx transfected cell tumors did not show growth inhibition upon treatment with dexamethasone. These results suggest that modulation of the antioxidant defense may play a role in dexamethasone-induced apoptosis and that Bcl-2 may prevent apoptosis by maintaining the level of critical antioxidant defense mechanisms including catalase. In addition, the thioredoxin study suggests that increased thioredoxin expression may result in a increased tumor growth through inhibition of spontaneous apoptosis and a decrease in the sensitivity of the tumor to drug-induced apoptosis.
dc.language.isoen_USen_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.subjectBiology, Molecular.en_US
dc.subjectBiology, Cell.en_US
dc.subjectHealth Sciences, Pharmacology.en_US
dc.titleModulation of the antioxidant defense during dexamethasone-induced apoptosis in WEHI7.2 mouse lymphoid cellsen_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
thesis.degree.grantorUniversity of Arizonaen_US
thesis.degree.leveldoctoralen_US
dc.identifier.proquest9806847en_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePharmacology & Toxicologyen_US
thesis.degree.namePh.D.en_US
dc.identifier.bibrecord.b37563725en_US
refterms.dateFOA2018-06-29T05:22:56Z
html.description.abstractThe modulation of the antioxidant defense during dexamethasone-induced apoptosis in WEHI7.2 cells mouse lymphoid cells was studied. When treated with dexamethasone, antioxidant defense transcripts including catalase, MnSOD, CuZnSOD, DT-diaphorase, GPX, and thioredoxin exhibited a progressive decrease over 24 hours (h) in apoptosis-sensitive wild-type WEHI7.2 and apoptosis-resistant bcl-2 transfected (W.Hb12) cells. Catalase activity was maintained and total SOD and DT-diaphorase activity showed smaller decreases following dexamethasone treatment of bcl-2 transfected cells. Treatment of wild-type and bcl-2 transfected WEHI7.2 cells with a catalase inhibitor, amino-triazole, was not sufficient to induce apoptosis. Antioxidants, including bovine liver catalase, bovine erythrocyte CuZnSOD, sodium selenite and Trolox, a water soluble vitamin E analogue, as well as hypoxia, inhibited dexamethasone-induced apoptosis. Transfection of the WEHI7.2 cells with catalase and thioredoxin resulted in a significant level of protection against dexamethasone-induced apoptosis. Thioredoxin-transfected cells were also protected from apoptosis induced by staurosporine, N-acetyl-sphingosine, etoposide and thapsigargin. When inoculated into severe combined immunodeficient (scid) mice the trx transfected cells formed tumors that showed increased growth compared to wild-type as well as bcl-2 transfected WEHI7.2 cells. The trx and bcl-2 transfected cell tumors both showed less spontaneous apoptosis than tumors formed by the wild-type cells. Unlike tumors formed by the wild-type and bcl-2 transfected WEHI7.2 cells, trx transfected cell tumors did not show growth inhibition upon treatment with dexamethasone. These results suggest that modulation of the antioxidant defense may play a role in dexamethasone-induced apoptosis and that Bcl-2 may prevent apoptosis by maintaining the level of critical antioxidant defense mechanisms including catalase. In addition, the thioredoxin study suggests that increased thioredoxin expression may result in a increased tumor growth through inhibition of spontaneous apoptosis and a decrease in the sensitivity of the tumor to drug-induced apoptosis.


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