{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T18:39:32Z","timestamp":1780079972543,"version":"3.54.0"},"reference-count":42,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1999,10,1]]},"abstract":"<jats:p>Mercury alters the function of proteins by reacting with cysteinyl sulfhydryl (SH<jats:sup>\u2212<\/jats:sup>) groups. The inorganic form (Hg<jats:sup>2+<\/jats:sup>) is toxic to epithelial tissues and interacts with various transport proteins including the Na<jats:sup>+<\/jats:sup>pump and Cl<jats:sup>\u2212<\/jats:sup>channels. In this study, we determined whether the Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup>cotransporter type 1 (NKCC1), a major ion pathway in secretory tissues, is also affected by mercurial substrates. To characterize the interaction, we measured the effect of Hg<jats:sup>2+<\/jats:sup>on ion transport by the secretory shark and human cotransporters expressed in HEK-293 cells. Our studies show that Hg<jats:sup>2+<\/jats:sup>inhibits Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup>cotransport, with inhibitor constant ( K<jats:sub>i<\/jats:sub>) values of 25 \u03bcM for the shark carrier (sNKCC1) and 43 \u03bcM for the human carrier. In further studies, we took advantage of species differences in Hg<jats:sup>2+<\/jats:sup>affinity to identify residues involved in the interaction. An analysis of human-shark chimeras and of an sNKCC1 mutant (Cys-697\u2192Leu) reveals that transmembrane domain 11 plays an essential role in Hg<jats:sup>2+<\/jats:sup>binding. We also show that modification of additional SH<jats:sup>\u2212<\/jats:sup>groups by thiol-reacting compounds brings about inhibition and that the binding sites are not exposed on the extracellular face of the membrane.<\/jats:p>","DOI":"10.1152\/ajpcell.1999.277.4.c684","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T22:40:56Z","timestamp":1514155256000},"page":"C684-C692","source":"Crossref","is-referenced-by-count":47,"title":["Inhibition of Na<sup>+<\/sup>-K<sup>+<\/sup>-2Cl<sup>\u2212<\/sup>cotransport by mercury"],"prefix":"10.1152","volume":"277","author":[{"given":"Steven C.","family":"Jacoby","sequence":"first","affiliation":[{"name":"Yale University School of Medicine, New Haven, Connecticut 06510; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Gagnon","sequence":"additional","affiliation":[{"name":"Nephrology Group, Department of Medicine, Faculty of Medicine, Research Center L\u2019H\u00f4tel-Dieu de Qu\u00e9bec, Laval University, Qu\u00e9bec, Canada G1R 2J6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Caron","sequence":"additional","affiliation":[{"name":"Nephrology Group, Department of Medicine, Faculty of Medicine, Research Center L\u2019H\u00f4tel-Dieu de Qu\u00e9bec, Laval University, Qu\u00e9bec, Canada G1R 2J6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Chang","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine, New Haven, Connecticut 06510; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Isenring","sequence":"additional","affiliation":[{"name":"Nephrology Group, Department of Medicine, Faculty of Medicine, Research Center L\u2019H\u00f4tel-Dieu de Qu\u00e9bec, Laval University, Qu\u00e9bec, Canada G1R 2J6"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00196939"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s002329900190"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.107.2.261"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1973.110"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1177\/019262339802600111"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.101.5.733"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1992.262.4.C1000"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)44299-2"},{"issue":"42","key":"B9","first-page":"R991","volume":"273","author":"Fujise H.","year":"1997","journal-title":"Am. 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