S-Nitrosation of proteins during D-galactosamine-induced cell death in human hepatocytes.
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.
López-Sánchez
Laura M
LM
Liver Research Unit, Hospital Universitario Reina Sofía, Córdoba, Spain.
Collado
Juan A
JA
Corrales
Fernando J
FJ
López-Cillero
Pedro
P
Montero
José L
JL
Fraga
Enrique
E
Serrano
Juan
J
De La Mata
Manuel
M
Muntané
Jordi
J
Rodríguez-Ariza
Antonio
A
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
D011506:Proteins; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D005688:Galactosamine; D053148:Caspase 3