Cysteine persulfides and polysulfides produced by exchange reactions with H₂S protect SH-SY5Y cells from methylglyoxal-induced toxicity through Nrf2 activation.

ABSTRACT: Many physiological functions of hydrogen sulfide (H₂S) have been reported in mammalian cells over the last 20 years. These physiological effects have been ascertained through in vitro treatment of cells with Na₂S or NaHS, both of which are precursors of H₂S. Since H₂S exists as HS^- in a neutral solution, a disulfide compound such as cystine could react with HS^- in culture medium as well as in the cell. This study demonstrated that after the addition of Na₂S solution into culture medium, HS^- was transiently generated and disappeared immediately through the reaction between HS^- and cystine to form cysteine persulfides and polysulfides in the culture medium (bound sulfur mixture: BS-Mix). Furthermore, we found that the addition of Na₂S solution resulted in an increase of intracellular cysteine persulfide levels in SH-SY5Y cells. This alteration in intracellular persulfide was also observed in cystine-free medium. Considering this reaction of HS^- as a precursor of BS-Mix, we highlighted the cytoprotective effect of Na₂S on human neuroblastoma SH-SY5Y cells against methylglyoxal (MG)-induced toxicity. BS-Mix produced with Na₂S in cystine-containing medium provided SH-SY5Y cells significant protective effect against MG-induced toxicity. However, the protective effect was attenuated in cystine-free medium. Moreover, we observed that Na₂S or BS-Mix activated the Keap1/Nrf2 system and increased glutathione (GSH) levels in the cell. In addition, the activation of Nrf2 is significantly attenuated in cystine-free medium. These results suggested that Na₂S protects SH-SY5Y cells from MG cytotoxicity through the activation of Nrf2, mediated by cysteine persulfides and polysulfides that were generated by Na₂S addition.

SUBMITTER: Koike S 

PROVIDER: S-EPMC5377440 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature