{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:49:11Z","timestamp":1791978551185,"version":"4.4.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2015,10,29]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Hydrogen sulfide (H\n                      <jats:sub>2<\/jats:sub>\n                      S) exhibits protective effects in various disease models including cerebral ischemia\u2013reperfusion (I\/R) injury. Nonetheless, mechanisms and identity of molecules responsible for neuroprotective effects of H\n                      <jats:sub>2<\/jats:sub>\n                      S remain incompletely defined. In the current study, we observed that thiosulfate, an oxidation product of H\n                      <jats:sub>2<\/jats:sub>\n                      S, mediates protective effects of an H\n                      <jats:sub>2<\/jats:sub>\n                      S donor compound sodium sulfide (Na\n                      <jats:sub>2<\/jats:sub>\n                      S) against neuronal I\/R injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      We observed that thiosulfate in cell culture medium is not only required but also sufficient to mediate cytoprotective effects of Na\n                      <jats:sub>2<\/jats:sub>\n                      S against oxygen glucose deprivation and reoxygenation of human neuroblastoma cell line (\n                      <jats:styled-content style=\"fixed-case\">SH<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">SY<\/jats:styled-content>\n                      5Y) and murine primary cortical neurons. Systemic administration of sodium thiosulfate (\n                      <jats:styled-content style=\"fixed-case\">STS<\/jats:styled-content>\n                      ) improved survival and neurological function of mice subjected to global cerebral I\/R injury. Beneficial effects of\n                      <jats:styled-content style=\"fixed-case\">STS<\/jats:styled-content>\n                      , as well as Na\n                      <jats:sub>2<\/jats:sub>\n                      S, were associated with marked increase of thiosulfate, but not H\n                      <jats:sub>2<\/jats:sub>\n                      S, in plasma and brain tissues. These results suggest that thiosulfate is a circulating \u201ccarrier\u201d molecule of beneficial effects of H\n                      <jats:sub>2<\/jats:sub>\n                      S. Protective effects of thiosulfate were associated with inhibition of caspase\u20103 activity by persulfidation at Cys163 in caspase\u20103. We discovered that an\n                      <jats:styled-content style=\"fixed-case\">SLC<\/jats:styled-content>\n                      13 family protein, sodium sulfate cotransporter 2 (\n                      <jats:styled-content style=\"fixed-case\">SLC<\/jats:styled-content>\n                      13A4, NaS\u20102), facilitates transport of thiosulfate, but not sulfide, across the cell membrane, regulating intracellular concentrations and thus mediating cytoprotective effects of Na\n                      <jats:sub>2<\/jats:sub>\n                      S and\n                      <jats:styled-content style=\"fixed-case\">STS<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      The protective effects of H\n                      <jats:sub>2<\/jats:sub>\n                      S are mediated by thiosulfate that is transported across cell membrane by NaS\u20102 and exerts antiapoptotic effects via persulfidation of caspase\u20103. Given the established safety track record, thiosulfate may be therapeutic against ischemic brain injury.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.115.002125","type":"journal-article","created":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T15:46:10Z","timestamp":1536939970000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":101,"title":["Thiosulfate Mediates Cytoprotective Effects of Hydrogen Sulfide Against Neuronal Ischemia"],"prefix":"10.1161","volume":"4","author":[{"given":"Eizo","family":"Marutani","sequence":"first","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine, 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