Mitochondrial Antioxidants, Protection Against Oxidative Stress, and the Role of Mitochondria in the Production of Reactive Oxygen Species

Persistent Link:
http://hdl.handle.net/10150/194490
Title:
Mitochondrial Antioxidants, Protection Against Oxidative Stress, and the Role of Mitochondria in the Production of Reactive Oxygen Species
Author:
Rogers, Kara Emilie
Issue Date:
2006
Publisher:
The University of Arizona.
Rights:
Copyright © 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.
Abstract:
Mitochondria serve as the major source of reactive oxygen species (ROS) production in cells resulting in antioxidant systems and cell signaling pathways that are unique to mitochondria. Thioredoxin-2 (Trx-2) is the mitochondrial member of the thioredoxin superfamily, and acts specifically to reduce the mitochondrial peroxidase, peroxiredoxin-3. It has been proposed that Trx-2 associates with cytochrome c, which functions in mitochondrial respiration and apoptosis. Homozygous Trx-2 deletion in mice is embryonic lethal and it is hypothesized here that Trx-2 lethality is caused by loss of mitochondrial function and oxidative stress. Results of experiments investigating mitochondrial integrity, cell viability, and ROS levels in Trx-2(-/-) mouse embryonic fibroblasts (MEFs), and results from Trx-2 siRNA MEFs, are similar to findings of knockouts in previously reported proteins that function in mitochondrial respiration and support the involvement of Trx-2 in this process. Mitochondrial ROS have also been implicated as major secondary messengers in cell signaling. Results reported here using cancer cells and cancer cells depleted of mitochondrial DNA, which consequently produce few ROS, have indicated that mitochondrial ROS produced in hypoxia are necessary for HRE and ARE activation, and are fundamental in the activation of SP-1 during reoxygenation. However, mitochondrial ROS are not required for HIF-1α protein expression in hypoxia, indicating a unique relationship between HIF-1α, hypoxia, and mitochondrial ROS.
Type:
text; Electronic Dissertation
Keywords:
Mitochondria; reactive oxygen species; antioxidant; siRNA
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Pharmacology & Toxicology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Powis, Garth
Committee Chair:
Powis, Garth

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleMitochondrial Antioxidants, Protection Against Oxidative Stress, and the Role of Mitochondria in the Production of Reactive Oxygen Speciesen_US
dc.creatorRogers, Kara Emilieen_US
dc.contributor.authorRogers, Kara Emilieen_US
dc.date.issued2006en_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.description.abstractMitochondria serve as the major source of reactive oxygen species (ROS) production in cells resulting in antioxidant systems and cell signaling pathways that are unique to mitochondria. Thioredoxin-2 (Trx-2) is the mitochondrial member of the thioredoxin superfamily, and acts specifically to reduce the mitochondrial peroxidase, peroxiredoxin-3. It has been proposed that Trx-2 associates with cytochrome c, which functions in mitochondrial respiration and apoptosis. Homozygous Trx-2 deletion in mice is embryonic lethal and it is hypothesized here that Trx-2 lethality is caused by loss of mitochondrial function and oxidative stress. Results of experiments investigating mitochondrial integrity, cell viability, and ROS levels in Trx-2(-/-) mouse embryonic fibroblasts (MEFs), and results from Trx-2 siRNA MEFs, are similar to findings of knockouts in previously reported proteins that function in mitochondrial respiration and support the involvement of Trx-2 in this process. Mitochondrial ROS have also been implicated as major secondary messengers in cell signaling. Results reported here using cancer cells and cancer cells depleted of mitochondrial DNA, which consequently produce few ROS, have indicated that mitochondrial ROS produced in hypoxia are necessary for HRE and ARE activation, and are fundamental in the activation of SP-1 during reoxygenation. However, mitochondrial ROS are not required for HIF-1α protein expression in hypoxia, indicating a unique relationship between HIF-1α, hypoxia, and mitochondrial ROS.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectMitochondriaen_US
dc.subjectreactive oxygen speciesen_US
dc.subjectantioxidanten_US
dc.subjectsiRNAen_US
thesis.degree.namePhDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmacology & Toxicologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorPowis, Garthen_US
dc.contributor.chairPowis, Garthen_US
dc.contributor.committeememberMcQueen, Charleneen_US
dc.contributor.committeememberVaillancourt, Richarden_US
dc.contributor.committeememberBriehl, Margareten_US
dc.contributor.committeememberEbbinghaus, Scoten_US
dc.identifier.proquest1514en_US
dc.identifier.oclc137356333en_US
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