Dissertation/Thesis Abstract

Thioredoxin-1: Identification of redox substrates and response to hyperoxia
by Floen, Miranda J., Ph.D., University of South Dakota, 2016, 204; 10132866
Abstract (Summary)

Bronchopulmonary dysplasia (BPD) is a serious respiratory complication for the preterm newborn characterized clinically by prolonged respiratory distress and histologically by alveolar simplification and decreased pulmonary vasculature. The development of BPD is well linked to oxidative stress suffered by the newborn as a result of a preterm fetal-neonatal transition, supplemental oxygen, infection, increased inflammation, and mechanical ventilation. Damage suffered by oxidative stress may be through direct mechanisms or through alteration of redox¬sensitive pathways involved in cell death, cell survival, differentiation, and proliferation. Redox¬sensitive modifications regulating protein function and redox-sensitive pathways have mainly been ascribed to oxidative modification of cysteine thiols. As their modification is critical for protein function, maintenance of the thiol redox status is crucial. Thioredoxin-1 (Trx1) functions in maintenance of thiol redox homeostasis, and its redox activity is intimately linked to antioxidant, cytoprotection, proliferation responses, and cytoprotection. While Trx1 targets of redox regulation have been identified, we hypothesize that additional protein may be redox regulated and that Trx1 target profiles may change during oxidative stress. Therefore a novel immunoprecipitation approach, identified as the substrate trap approach, was developed to identify Trx1 targets. The following demonstrates the use of the substrate trap approach for identification of Trx1 redox targets and further application of the approach to identify alterations in target profiles in response to oxidative stress. Use of nuclear targeted substrate trap was successfully employed to enrich from nuclear Trx1 targets. As a final component the characterization of the Trx1 system in mouse from late embryonic development through the first week of life animals were exposed to room air or hyperoxia (model of BPD). Characterization indicates impairment of the Trx1 system in response to hyperoxic injury. As Trx1 is known to regulate proliferation, cell death, survival, differentiation pathways, impairment of the Trx1 system during early neonatal development may potentiate hyperoxic injury and alterations in lung development. Better understanding of Trx1 interactions occur through the substrate trap in a physiological model of BPD will help elucidate redox-signaling pathways involved in BPD pathogenesis.

Indexing (document details)
Advisor: Vitiello, Peter F.
Commitee: Baack, Michelle, Huber, Victor, Pearce, David, Schlenker, Evelyn
School: University of South Dakota
Department: Basic Biomedical Sciences
School Location: United States -- South Dakota
Source: DAI-B 77/12(E), Dissertation Abstracts International
Subjects: Molecular biology, Cellular biology
Keywords: Bronchopulmonary dysplasia, Hyperoxia, Thioredoxin
Publication Number: 10132866
ISBN: 9781339913407
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