title: S-Nitrosation of proteins during D-galactosamine-induced cell death in human hepatocytes.
abstract: Nitric oxide (NO) participates in the cell death induced by d-Galactosamine (d-GalN) in hepatocytes, and NO-derived reactive oxygen intermediates are critical contributors to protein modification and hepatocellular injury. It is anticipated that S-nitrosation of proteins will participate in the mechanisms leading to cell death in d-GalN-treated human hepatocytes. In the present study, d-GalN-induced cell death was related to augmented levels of NO production and S-nitrosothiol (SNO) content. The biotin switch assay confirmed that d-GalN increased the levels of S-nitrosated proteins in human hepatocytes. S-nitrosocysteine (CSNO) enhanced protein S-nitrosation and altered cell death parameters that were related to S-nitrosation of the executioner caspase-3. Fifteen S-nitrosated proteins participating in metabolism, antioxidative defense and cellular homeostasis were identified in human hepatocytes treated with CSNO. Among them, seven were also identified in d-GalN-treated hepatocytes. The results here reported underline the importance of the alteration of SNO homeostasis during d-GalN-induced cell death in human hepatocytes.
authors.affiliation: Liver Research Unit, Hospital Universitario Reina Sofía, Córdoba, Spain.
authors.forename: Laura M
authors.initials: LM
authors.lastname: López-Sánchez
authors.forename: Juan A
authors.initials: JA
authors.lastname: Collado
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Corrales
authors.forename: Pedro
authors.initials: P
authors.lastname: López-Cillero
authors.forename: José L
authors.initials: JL
authors.lastname: Montero
authors.forename: Enrique
authors.initials: E
authors.lastname: Fraga
authors.forename: Juan
authors.initials: J
authors.lastname: Serrano
authors.forename: Manuel
authors.initials: M
authors.lastname: De La Mata
authors.forename: Jordi
authors.initials: J
authors.lastname: Muntané
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez-Ariza
mesh_terms: D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D005260:Female; D005688:Galactosamine / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D015538:Nitrosation; D011506:Proteins / Q000378:metabolism*; D026403:S-Nitrosothiols / Q000378:metabolism
chemical_list: D011506:Proteins; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D005688:Galactosamine; D053148:Caspase 3