title: Oxidative stress-induced proteome alterations target different cellular pathways in human myoblasts.
abstract: Although increased oxidative stress has been associated with the impairment of proliferation and function of adult human muscle stem cells, proteins either involved in the stress response or damaged by oxidation have not been identified. A parallel proteomics approach was performed for analyzing the protein expression profile as well as proteins preferentially oxidized upon hydrogen peroxide-induced oxidative stress. Fifteen proteins involved in the oxidative stress response were identified. Among them, protein spots identified as peroxiredoxins 1 and 6, glyceraldehyde-3-phosphate dehydrogenase, and α-enolase were shifted to a more acidic isoelectric point upon oxidative stress, indicating posttranslational modifications. Oxidized proteins were evidenced by immunodetection of derivatized carbonyl groups followed by identification by mass spectrometry. The carbonylated proteins identified are mainly cytosolic and involved in carbohydrate metabolism, cellular assembly, cellular homeostasis, and protein synthesis and degradation. Pathway analysis revealed skeletal and muscular disorders, cell death, and cancer-related as the main molecular networks altered. Interestingly, these pathways were focused on two distinct proteins: p53 for altered protein expression and huntingtin for increased protein carbonylation. This study emphasizes the importance of performing analysis addressing different aspects of the cellular proteome to have a more accurate view of their changes upon stress.
authors.affiliation: Laboratoire de Biologie Cellulaire du Vieillissement, UR4, Université Pierre et Marie Curie-Paris 6, 75252 Paris Cedex 05, France.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Baraibar
authors.forename: Janek
authors.initials: J
authors.lastname: Hyzewicz
authors.forename: Adelina
authors.initials: A
authors.lastname: Rogowska-Wrzesinska
authors.forename: Romain
authors.initials: R
authors.lastname: Ladouce
authors.forename: Peter
authors.initials: P
authors.lastname: Roepstorff
authors.forename: Vincent
authors.initials: V
authors.lastname: Mouly
authors.forename: Bertrand
authors.initials: B
authors.lastname: Friguet
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D003198:Computer Simulation; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein; D006861:Hydrogen Peroxide / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D054465:Peroxiredoxin VI / Q000378:metabolism; D054464:Peroxiredoxins / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D050050:Protein Carbonylation; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D020543:Proteome; D016159:Tumor Suppressor Protein p53; D006861:Hydrogen Peroxide; C515940:PRDX1 protein, human; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010751:Phosphopyruvate Hydratase