Sulfite protects neurons from oxidative stress

Background and Purpose Hydrogen sulfide (H2S) and polysulfides (H2Sn) are signalling molecules that mediate various physiological responses including cytoprotection. Their oxidized metabolite sulfite (SO32-) is found in blood and tissues. However, its physiological role remains unclear. In this study, we investigated the cytoprotective effect of sulfite on neurons exposed to oxidative stress caused by high concentrations of the neurotransmitter glutamate, known as oxytosis. Experimental Approach Concentrations of sulfite as well as those of cysteine and GSH in rats were measured by HPLC. Cytoprotective effects of sulfite on primary cultures of rat neurons against oxytosis was examined by WST-8 cytoprotective and LDH cytotoxicity assays and compared with that of H2S, H2Sn and thiosulfate. Key Results Free sulfite, present at approximately 2 mu M in the rat brain, converts cystine to cysteine more efficiently than H2S and H2Sn and facilitates transport of cysteine into cells. Physiological concentrations of sulfite protected neurons from oxytosis and were accompanied by increased intracellular concentrations of cysteine and GSH probably due to converting extracellular cystine to cysteine, more efficiently than H2S and H2Sn. In contrast, thiosulfate only slightly protected neurons from oxyt