NDLI: Selective targeting of the cysteine proteome by thioredoxin and glutathione redox systems.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Go, Young-Mi Roede, James R. Walker, Douglas I. Duong, Duc M. Seyfried, Nicholas T. Orr, Michael Liang, Yongliang Pennell, Kurt D. Jones, Dean P.
Description	Author Affiliation: Go YM ( Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine.)
Abstract	Thioredoxin (Trx) and GSH are the major thiol antioxidants protecting cells from oxidative stress-induced cytotoxicity. Redox states of Trx and GSH have been used as indicators of oxidative stress. Accumulating studies suggest that Trx and GSH redox systems regulate cell signaling and metabolic pathways differently and independently during diverse stressful conditions. In the current study, we used a mass spectrometry-based redox proteomics approach to test responses of the cysteine (Cys) proteome to selective disruption of the Trx- and GSH-dependent systems. Auranofin (ARF) was used to inhibit Trx reductase without detectable oxidation of the GSH/GSSG couple, and buthionine sulfoximine (BSO) was used to deplete GSH without detectable oxidation of Trx1. Results for 606 Cys-containing peptides (peptidyl Cys) showed that 36% were oxidized more than 1.3-fold by ARF, whereas BSO-induced oxidation of peptidyl Cys was only 10%. Mean fold oxidation of these peptides was also higher by ARF than BSO treatment. Analysis of potential functional pathways showed that ARF oxidized peptides associated with glycolysis, cytoskeleton remodeling, translation and cell adhesion. Of 60 peptidyl Cys oxidized due to depletion of GSH, 41 were also oxidized by ARF and included proteins of translation and cell adhesion but not glycolysis or cytoskeletal remodeling. Studies to test functional correlates showed that pyruvate kinase activity and lactate levels were decreased with ARF but not BSO, confirming the effects on glycolysis-associated proteins are sensitive to oxidation by ARF. These data show that the Trx system regulates a broader range of proteins than the GSH system, support distinct function of Trx and GSH in cellular redox control, and show for the first time in mammalian cells selective targeting peptidyl Cys and biological pathways due to deficient function of the Trx system.
File Format	HTM / HTML
ISSN	15359476
e-ISSN	15359484
DOI	10.1074/mcp.M113.030437
Journal	Molecular & Cellular Proteomics
Issue Number	11
Volume Number	12
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2013-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Proteomics Cysteine Metabolism Glutathione Thioredoxins Antioxidants Auranofin Pharmacology Buthionine Sulfoximine Enzyme Inhibitors Glutathione Disulfide Ht29 Cells Metabolic Networks And Pathways Oxidation-reduction Proteome Proteomics Signal Transduction Thioredoxin-disulfide Reductase Antagonists & Inhibitors Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Medicine Analytical Chemistry Molecular Biology Biochemistry

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