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• W2091722281 endingPage "1874" @default.
• W2091722281 startingPage "1863" @default.
• W2091722281 abstract "The susceptibility of neuronal cells to nitric oxide (NO) is a key issue in NO-mediated neurotoxicity. However, the underlying mechanism remains unclear. As a cyclic guanosine monophosphate (cGMP)-independent NO signaling pathway, S-nitrosylation (or S-nitrosation) has been suggested to occur as a post-translational modification in parallel with O-phosphorylation. The underlying mechanism of the involvement of protein S-nitrosylation in the susceptibility of neuronal cells to NO has been little investigated. In this study, we focused on the role of S-nitrosothiols (RSNO) in the susceptibility of a cerebellar cell line R2 to NO. Our results showed the following: (i) S-nitrosoglutathione (GSNO) induced a burst of RSNO in GSH-depleted R2 cells, the majority of which were primarily contributed by the S-nitrosylation of proteins (Pro-SNOs), and was followed by severe neuronal necrosis; (ii) the elevation in the level of Pro-SNOs resulted from a dysfunction of S-nitroglutathione reductase (GSNOR) as a result of its substrate, GSNO, being unavailable in GSH-depleted cells. In the meantime, the suppression of GSNOR increased NO-mediated neurotoxicity in R2 cells, as well as in cerebellar granule neurons; (iii) Our results also demonstrate that the burst of RSNO is the checkpoint of cell fate: if RSNO can be reduced to free thiol proteins, cells will survive; if they are further oxidized, cells will die; and (iv) GSH-ethyl ester and Vitamin C protected R2 cells against GSNO neurotoxicity through two distinct mechanisms: by inhibiting the elevation of Pro-SNOs and by reducing Pro-SNOs to free thiol proteins, respectively. A novel mechanism underlying the susceptibility of neuronal cells to NO is proposed and some potential strategies to prevent the NO-mediated neurotoxicity are discussed." @default.
• W2091722281 created "2016-06-24" @default.
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• W2091722281 date "2007-04-15" @default.
• W2091722281 modified "2023-10-14" @default.
• W2091722281 title "A novel mechanism underlying the susceptibility of neuronal cells to nitric oxide: the occurrence and regulation of protein<i>S</i>-nitrosylation is the checkpoint" @default.
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• W2091722281 doi "https://doi.org/10.1111/j.1471-4159.2007.04651.x" @default.
• W2091722281 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17767703" @default.
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