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.
| Identifer | oai:union.ndltd.org:unt.edu/info:ark/67531/metadc1808366 |
| Date | 05 1900 |
| Creators | Pandey, Prajita |
| Contributors | Shulaev, Vladimir, Kunz, Daniel A., 1949-, Prokai, Laszlo, Venables, Barney, Azad, Rajeev, Wang, Xiaoqiang |
| Publisher | University of North Texas |
| Source Sets | University of North Texas |
| Language | English |
| Detected Language | English |
| Type | Thesis or Dissertation |
| Format | xi, 185 pages : illustrations (some color), Text |
| Rights | Public, Pandey, Prajita, Copyright, Copyright is held by the author, unless otherwise noted. All rights Reserved. |
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