title: Redox status in a model of cancer stem cells.
abstract: Reversible oxidation of Cys residues is a crucial element of redox homeostasis and signaling. According to a popular concept in oxidative stress signaling, the oxidation of targets of signals can only take place following an overwhelming of the cellular antioxidant capacity. This concept, however, ignores the activation of feedback mechanisms possibly leading to a paradoxical effect. In a model of cancer stem cells (CSC), stably overexpressing the TAZ oncogene, we observed that the increased formation of oxidants is associated with a globally more reduced state of proteins. Redox proteomics revealed that several proteins, capable of undergoing reversible redox transitions, are indeed more reduced while just few are more oxidized. Among the proteins more oxidized, G6PDH emerges as both more expressed and activated by oxidation. This accounts for the observed more reduced state of the NADPH/NADP+couple. The dynamic redox flux generating this apparently paradoxical effect is rationalized in a computational system biology model highlighting the crucial role of G6PDH activity on the rate of redox transitions eventually leading to the reduction of reversible redox switches.
authors.affiliation: Department of Molecular Medicine, University of Padova, Viale G.Colombo 3, 35121 Padova, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Zaccarin
authors.affiliation: Department of Molecular Medicine, University of Padova, Viale G.Colombo 3, 35121 Padova, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bosello-Travain
authors.affiliation: Department of Molecular Medicine, University of Padova, Viale G.Colombo 3, 35121 Padova, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Di Paolo
authors.affiliation: Department of Molecular Medicine, University of Padova, Viale G.Colombo 3, 35121 Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Falda
authors.affiliation: Department of Molecular Medicine, University of Padova, Viale G.Colombo 3, 35121 Padova, Italy.
authors.forename: Matilde
authors.initials: M
authors.lastname: Maiorino
authors.affiliation: Department of Molecular Medicine, University of Padova, Viale G.Colombo 3, 35121 Padova, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Miotto
authors.affiliation: Department of Molecular Medicine, University of Padova, Viale G.Colombo 3, 35121 Padova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Piccolo
authors.affiliation: Department of Molecular Medicine, University of Padova, Viale G.Colombo 3, 35121 Padova, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Roveri
authors.affiliation: Department of Molecular Medicine, University of Padova, Viale G.Colombo 3, 35121 Padova, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Ursini
authors.affiliation: Department of Molecular Medicine, University of Padova, Viale G.Colombo 3, 35121 Padova, Italy.
authors.forename: Rina
authors.initials: R
authors.lastname: Venerando
authors.affiliation: Department of Molecular Medicine, University of Padova, Viale G.Colombo 3, 35121 Padova, Italy. Electronic address: stefano.toppo@unipd.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Toppo
mesh_terms: D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D054477:Glutaredoxins / Q000378:metabolism; D006801:Humans; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000166:cytology*; D009711:Nucleotides / Q000235:genetics; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D040901:Proteomics; D011725:Pyridines / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D054477:Glutaredoxins; D009711:Nucleotides; D011725:Pyridines; D017382:Reactive Oxygen Species; D013879:Thioredoxins; D005954:Glucosephosphate Dehydrogenase; D013880:Thioredoxin-Disulfide Reductase; C023666:pyridine; D010100:Oxygen
keywords: Cancer stem cells; Protein thiols; Redox proteomics; Redox state