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Cover for THE REGULATORY ROLES OF GAMMA INTERFERON INDUCIBLE LYSOSOMAL THIOL REDUCTASE (GILT) IN CELLULAR REDOX HOMEOSTASIS
dc.contributor.advisorMaric, Majaen
dc.creatoren
dc.date.accessioned2013-05-17T17:44:29Zen
dc.date.created2011en
dc.date.issueden
dc.date.submitted01/01/2011en
dc.identifier.otherAPT-BAG: georgetown.edu.10822_558137.tar;APT-ETAG: c5fd13d793d052198ac7ce31b101fada; APT-DATE: 2017-10-30_10:43:39en-US
dc.identifier.urien
dc.descriptionPh.D.en
dc.description.abstractRedox regulation is critical for a number of cellular functions and has been implicated in the etiology and progression of cardiovascular diseases, neurodegenerative diseases, and cancer. It has been shown that in the absence of Gamma-interferon Inducible Lysosomal Thiol reductase (GILT), cells experience moderate oxidative stress indicated by increased production of reactive oxygen species and reduced expression of mitochondrial manganese superoxide dismutase (SOD2). In the current study, we further elucidate the role of GILT in homeostatic regulation in response to oxidative stress. We show that GILT-deficient fibroblasts exhibit a decreased level of reduced glutathione, an increase in the ratio of oxidized (GSSG) vs. reduced (GSH) forms of glutathione and an accumulation of dysfunctional mitochondria. Redox-sensitive pathways involving Erk1/2 activation and high mobility group box 1 (HMGB1) protein cytosolic translocation are both activated and associated with an increased autophagy in GILT -/- fibroblasts. We hypothesize that the absence of GILT triggers these intracellular changes that ultimately result in the degradation of the damaged mitochondria and mitochondrial SOD2 in the absence of GILT. To our knowledge, this is the first time that a lysosomal enzyme has been implicated in maintenance of cellular redox homeostasis.en
dc.formatPDFen
dc.format.extent128 leavesen
dc.languageenen
dc.publisherGeorgetown Universityen
dc.sourceGeorgetown University-Graduate School of Arts & Sciencesen
dc.sourceMicrobiology & Immunologyen
dc.subjectAutophagyen
dc.subjectGILTen
dc.subjectglutathioneen
dc.subjectredoxen
dc.subjectROSen
dc.subjectSOD2en
dc.subject.lcshImmunologyen
dc.subject.lcshCytologyen
dc.subject.lcshBiochemistryen
dc.subject.otherImmunologyen
dc.subject.otherCellular Biologyen
dc.subject.otherBiochemistryen
dc.titleTHE REGULATORY ROLES OF GAMMA INTERFERON INDUCIBLE LYSOSOMAL THIOL REDUCTASE (GILT) IN CELLULAR REDOX HOMEOSTASISen
dc.typethesisen
gu.embargo.lift-date2015-05-17en
gu.embargo.terms2-yearsen


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