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Nrf2 activation but not vitamin C treatment promotes proteostatic maintenance during an oxidative challenge

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dc.contributor.authorEhrlicher, Sarah E., author
dc.contributor.authorMiller, Benjamin F., advisor
dc.contributor.authorHamilton, Karyn L., advisor
dc.contributor.authorMelby, Christopher, committee member
dc.date.accessioned2016-07-13T14:50:24Z
dc.date.available2017-07-12T06:30:24Z
dc.date.issued2016
dc.description.abstractImproved proteostasis may be a mechanism of stress resistance, and it is likely that the increased protein turnover with exercise training contributes to adaptation to stress. Exogenous antioxidant treatments such as vitamin C (VitC) target the detrimental effects of reactive oxygen species (ROS), but may simultaneously prevent the beneficial redox signaling associated with exercise. A possible alternative strategy to prevent oxidative damage while permitting redox-sensitive signaling is to increase endogenous antioxidants. The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) increases the transcription of endogenous antioxidants by binding to the antioxidant response element in the promoter region of target genes. Protandim (Pro, LifeVantage), a combination of five phytochemicals, activates Nrf2 by increasing its translocation to the nucleus. We hypothesized that, compared to VitC, treatment with the Nrf2 activator Pro would not blunt ROS induced proteostatic maintenance. To mimic ROS signaling, C2C12 myoblasts were treated with H2O2. Treatment occurred alone or in combination with either VitC or Pro. Deuterium oxide labeling was used to measure protein synthesis in the mitochondrial and cytosolic cell fractions after 2, 4, 8, and 12 hours of treatment. Simultaneously cell proliferation was measured by deuterium incorporation into DNA. Compared to the untreated control, H2O2 alone increased DNA synthesis but did not increase mitochondrial protein synthesis, resulting in decreased proteostasis. Compared to H2O2 alone, Pro decreased protein synthesis in both cytosolic and mitochondrial fractions. However, Pro also decreased DNA synthesis. This resulted in a greater protein to DNA ratio suggesting maintenance of proteostasis. VitC with H2O2 increased DNA synthesis and decreased proteostasis, similar to H2O2 treatment alone. From these data, it appears that although treatment with exogenous antioxidants increases proliferation, activation of Nrf2 maintains mitochondrial protein synthesis despite a reduction in proliferation. Further study into the role of Nrf2 in improving mitochondrial proteostasis to promote stress resistance is warranted.
dc.format.mediumborn digital
dc.format.mediummasters theses
dc.identifier.urihttp://hdl.handle.net/10217/173519
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.titleNrf2 activation but not vitamin C treatment promotes proteostatic maintenance during an oxidative challenge
dc.typeText
dcterms.embargo.expires2017-07-12
dcterms.embargo.terms2017-07-12
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineHealth and Exercise Science
thesis.degree.grantorColorado State University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science (M.S.)

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