Thesis (Ph. D.) -- California Institute of Technology, 2010. / Title from home page (viewed 04/05/10). Advisor and committee chair names found in the thesis' metadata record in the digital repository. Includes bibliographical references.

The early signaling mechanism(s) that control oxidant perception and signal transduction leading to activation of the antioxidant defense response and survival mechanisms tailored toward specific oxidative insult remains unknown. Here, we identified early changes in metabolome and proteome of S. cerevisiae in response to hydrogen peroxide, menadione, cumene hydroperoxide, and diamide. Firstly, global untargeted LC–MS/MS analysis allowed us to identify 196 proteins in response to hydrogen peroxide, 569 proteins in response to cumene hydroperoxide, 369 proteins in response to menadione and 207 proteins in response to diamide that were significantly regulated at 3 min after exposure. We revealed that each oxidant triggered unique signaling mechanisms associated with survival and repair mechanisms as early as 3 minutes of post treatment with a set of proteins that uniquely responded to the particular oxidant. In addition, our comprehensive pathway analysis revealed signaling pathways and the molecular players that are regulated globally by all oxidants at early time points namely Ran, mTOR, Rho, and eIF2. Additionally, we analyzed metabolic response using targeted GC-MS/MS that allowed us to identity 35 metabolites that were consistently detected in all samples at 3 min of exposure. These metabolites showed distinct response to the four oxidants in carbohydrate metabolism, tricarboxylic acid, amino acid metabolism and glutathione cycle. Furthermore, temporal analysis showed targeted metabolites significantly regulated at different time points by different oxidants suggesting specificity in the response to oxidants having different mode of actions.

Thesis (Ph. D.)--West Virginia University, 2006. / Title from document title page. Document formatted into pages; contains xii, 203 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.

published_or_final_version / abstract / Biological Sciences / Doctoral / Doctor of Philosophy

No description available.

No description available.

No description available.

No description available.

Transplantation is an acceptable treatment for end-stage lung and liver disease patients. In lung transplantation, long-term survival is limited due to Bronchiolitis Obliterans Syndrome (BOS) and in liver transplantation, Hepatitis C Virus (HCV) disease recurrence significantly impacts long-term survival. Treatment options are limited and often not successful. It is therefore important to conduct research on the factors contributing to the pathogenesis and disease severity of BOS and HCV to improve our understanding of the mechanisms and potentially reduce morbidity and mortality. Several factors may play a role. The focus of this thesis is to assess the role of Oxidative Stress (OxS) and nutrition on these patient populations. BOS is a frequent complication of lung transplantation. OxS may contribute to its pathogenesis and induce further tissue injury and inflammation. OxS can be influenced by several factors including nutrition. The cross-sectional study showed that BOS lung recipients have elevated markers of OxS in their Bronchoalveolar Lavage Fluid (BALF) compared to those without BOS. However, there was no difference in nutritional factors potentially affecting OxS. HCV reinfection post transplant is universal, significantly increasing morbidity and mortality. OxS is involved in the pathogenesis of chronic HCV but its role in HCV disease recurrence is unknown. A first study determined whether HCV liver recipients (HCV-LT) were more oxidatively stressed when compared to controls or HCV non-transplant patients. A second study assessed OxS at six-and 12 months post transplant and compared results between those with and without recurrence. The results showed that HCV-LT were more oxidatively stressed, vitamin A intakes were significantly lower and plasma gamma- tocopherol was significantly higher in HCV-LT. Additionally, those with recurrence were more oxidatively stressed at six-months (before recurrence) and 12 months compared to those without recurrence. No differences were seen regarding nutrition parameters. These results suggest that OxS is present in transplant recipients but that nutritional factors do not play a significant role. Other causes of OxS likely play a more significant role such as the presence of inflammation due to immunological reactions associated with BOS and the generation of reactive oxygen species (ROS/RNS) seen in patients with HCV disease.

No description available.