S-Nitrosation of proteins during D-galactosamine-induced cell death in human hepatocytes |
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Authors: | López-Sánchez Laura M Collado Juan A Corrales Fernando J López-Cillero Pedro Montero José L Fraga Enrique Serrano Juan De La Mata Manuel Muntané Jordi Rodríguez-Ariza Antonio |
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Institution: | Liver Research Unit, Hospital Universitario Reina Sofía, Córdoba, Spain. |
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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. |
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