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Selenite serves as an antagonist of mercury toxicity\u2019 but the molecular mechanism of detoxification is not clear. Inhibition of the selenoen\u2010zyme thioredoxin reductase (TrxR) is a suggested mechanism of toxicity. Here, we demonstrated enhanced inhibition of activity by inorganic and organic mercury compounds in NADPH\u2010reduced TrxR, consistent with binding of mercury also to the active site selenolthiol. On treatment with 5 \u00b5M selenite and NADPH\u2019 TrxR inactivated by HgCl\n                    <jats:sub>2<\/jats:sub>\n                    displayed almost full recovery of activity. Structural analysis indicated that mercury was complexed with TrxR\u2019 but enzyme\u2010generated selenide removed mercury as mercury selenide\u2019 regenerating the active site selenocysteine and cysteine residues required for activity. The antagonistic effects on TrxR inhibition were extended to endogenous antioxidants\u2019 such as GSH, and clinically used exogenous chelating agents BAL\u2019 DMPS\u2019 DMSA\u2019 and \u03b1\u2010lipoic acid. Consistent with the\n                    <jats:italic>in vitro<\/jats:italic>\n                    results\u2019 recovery of TrxR activity and cell viability by selenite was observed in HgCl\n                    <jats:sub>2<\/jats:sub>\n                    \u2010treated HEK 293 cells. These results stress the role of TrxR as a target of mercurials and provide the mechanism of selenite as a detoxification agent for mercury poisoning.\u2014Carvalho, C. M. L., Lu, J., Zhang, X., Arn\u00e9r, E. S. J., Holmgren, A. Effects of selenite and chelating agents on mammalian thiore\u2010doxin reductase inhibited by mercury: implications for treatment of mercury poisoning.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    25, 370\u2013381 (2011).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.10-157594","type":"journal-article","created":{"date-parts":[[2010,9,1]],"date-time":"2010-09-01T23:02:57Z","timestamp":1283382177000},"page":"370-381","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":111,"title":["Effects of selenite and chelating agents on mammalian thioredoxin reductase inhibited by mercury: implications for treatment of mercury poisoning"],"prefix":"10.1096","volume":"25","author":[{"given":"Cristina M. L.","family":"Carvalho","sequence":"first","affiliation":[{"name":"Research Institute for Medicines and Pharmaceutical Sciences Faculty of Pharmacy University of Lisbon Lisbon Portugal"},{"name":"Division of Biochemistry Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden"}]},{"given":"Jun","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Biochemistry Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Biochemistry Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden"}]},{"given":"Elias S. J.","family":"Arn\u00e9r","sequence":"additional","affiliation":[{"name":"Division of Biochemistry Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden"}]},{"given":"Arne","family":"Holmgren","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines and Pharmaceutical Sciences Faculty of Pharmacy University of Lisbon Lisbon Portugal"}]}],"member":"311","published-online":{"date-parts":[[2010,9,1]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jtra.10050"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408440600845619"},{"key":"e_1_2_6_4_1","volume-title":"Mercury","author":"World Health Organization Regional Office for Europe","year":"2000"},{"key":"e_1_2_6_5_1","unstructured":"World Health Organization(2003)Summary and conclusions of the sixty\u2010first meeting of the Joint FAO\/WHO Expert Committee on Food Additives (JECFA). 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