title: Comparative proteomic analysis of thiol proteins in the liver after oxidative stress induced by diethylnitrosamine.
abstract: Conversion of protein -SH groups to disulfides is an early event during protein oxidation, which has prompted great interest in the study of thiol proteins. Chemical carcinogenesis is strongly associated with the formation of reactive oxygen species (ROS). The goal of this study was to detect thiol proteins that are sensitive to ROS generated during diethylnitrosamine (DEN) metabolism in the rat liver. DEN has been widely used to induce experimental hepatocellular carcinoma. We used modified redox-differential gel electrophoresis (redox-DIGE method) and mass spectrometry MALDI-TOF/TOF to identify differential oxidation protein profiles associated with carcinogen exposure. Our analysis revealed a time-dependent increase in the number of oxidized thiol proteins after carcinogen treatment; some of these proteins have antioxidant activity, including thioredoxin, peroxirredoxin 2, peroxiredoxin 6 and glutathione S-transferase alpha-3. According to functional classifications, the identified proteins in our study included chaperones, oxidoreductases, activity isomerases, hydrolases and other protein-binding partners. This study demonstrates that oxidative stress generated by DEN tends to increase gradually through DEN metabolism, causes time-dependent necrosis in the liver and has an oxidative effect on thiol proteins, thereby increasing the number of oxidized thiol proteins. Furthermore, these events occurred during the hepatocarcinogenesis initiation period.
authors.affiliation: Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, D.F. 07360, México. Electronic address: abdi2401@hotmail.com.
authors.forename: Diana I
authors.initials: DI
authors.lastname: Aparicio-Bautista
authors.forename: Julio I
authors.initials: JI
authors.lastname: Pérez-Carreón
authors.forename: Nora
authors.initials: N
authors.lastname: Gutiérrez-Nájera
authors.forename: Juan P
authors.initials: JP
authors.lastname: Reyes-Grajeda
authors.forename: Jaime
authors.initials: J
authors.lastname: Arellanes-Robledo
authors.forename: Verónica R
authors.initials: VR
authors.lastname: Vásquez-Garzón
authors.forename: Mónica N
authors.initials: MN
authors.lastname: Jiménez-García
authors.forename: Saúl
authors.initials: S
authors.lastname: Villa-Treviño
mesh_terms: D000477:Alkylating Agents / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004052:Diethylnitrosamine / Q000009:adverse effects* / Q000494:pharmacology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009336:Necrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D051381:Rats; D011916:Rats, Inbred F344; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D000477:Alkylating Agents; D000975:Antioxidants; D020543:Proteome; D013438:Sulfhydryl Compounds; D004052:Diethylnitrosamine; D010088:Oxidoreductases
keywords: DIGE; Diethylnitrosamine; Oxidation; ROS; Thiol protein