title: Redox proteomics reveal stress responsive proteins linking peroxiredoxin-1 status in glioma to chemosensitivity and oxidative stress.
abstract: The combined deletion of chromosomal arms 1p and 19q has been described as a prognostic marker for oligodendroglial tumors. These tumors show a better response to chemotherapy and radiotherapy. Recently, we found a lower abundance of peroxiredoxin 1 (PRDX1) in oligodendroglial tumors with 1p/19q deletion, suggesting a potential role of this enzyme in the clearance of therapy induced reactive oxygen species (ROS). Here, we confirmed the importance of PRDX1 in tumor cell survival by PRDX1 knockdown and overexpression in A-172 cells treated with the alkylating agent bis-chloroethyl nitrosourea (BCNU). Overexpression of PRDX1 resulted in a higher resistance of cells to BCNU treatment. In addition, BCNU challenged cells showed higher levels of ROS in PRDX1 knockdown cells. We applied a modified version of the redox two dimensional difference gel electrophoresis approach to analyze ROS mediated effects on protein thiols after BCNU treatment by labeling protein thiols with fluorescent dyes. Altogether eleven proteins were identified showing PRDX1 dependent altered labeling, many of them have been previously linked to stress response processes. Furthermore, 30 additional potentially redox active proteins were identified. The majority of them is involved in therapy associated processes like cellular stress response, DNA damage and regulation of cell death and therewith suggests that tumor cells maintain a network of redox sensitive proteins to escape chemotherapy. This article is part of a Special Issue entitled: Medical Proteomics.
authors.affiliation: Molecular Proteomics Laboratory, BMFZ, Universität Düsseldorf, Germany. Electronic address: gereon.poschmann@hhu.de.
authors.forename: Gereon
authors.initials: G
authors.lastname: Poschmann
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum, Germany; Roche Diagnostics GmbH, Mannheim, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Grzendowski
authors.affiliation: Molecular Proteomics Laboratory, BMFZ, Universität Düsseldorf, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Stefanski
authors.affiliation: Molecular Proteomics Laboratory, BMFZ, Universität Düsseldorf, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Bruns
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum, Germany; Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Dortmund, Germany.
authors.forename: Helmut Erich
authors.initials: HE
authors.lastname: Meyer
authors.affiliation: Molecular Proteomics Laboratory, BMFZ, Universität Düsseldorf, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Stühler
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D002330:Carmustine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004249:DNA Damage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D017353:Gene Deletion; D005910:Glioma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; C515940:PRDX1 protein, human; D054464:Peroxiredoxins; D002330:Carmustine
keywords: Cancer; Chemoresistance; Glioma; PRDX1; Redox process; Thiol