{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:24:16Z","timestamp":1790385856527,"version":"4.1.0"},"reference-count":54,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2011,10,12]],"date-time":"2011-10-12T00:00:00Z","timestamp":1318377600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Toxicol"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:p>\n                    Here, we investigated thiol-redox-mediated phospholipase D (PLD) signaling as a mechanism of mercury cytotoxicity in mouse aortic endothelial cell (MAEC) in vitro model utilizing the novel lipid-soluble thiol-redox antioxidant and heavy metal chelator, N, N\u2032-bis(2-mercaptoethyl)isophthalamide (NBMI) and the novel PLD-specific inhibitor, 5-fluoro-2-indolyl des-chlorohalopemide (FIPI). Our results demonstrated ( i) mercury in the form of mercury(II) chloride, methylmercury, and thimerosal induced PLD activation in a dose- and time-dependent manner; ( ii) NBMI and FIPI completely attenuated mercury- and oxidant-induced PLD activation; ( iii) mercury induced upstream phosphorylation of extracellular-regulated kinase 1\/2 (ERK1\/2) leading to downstream threonine phosphorylation of PLD\n                    <jats:sub>1<\/jats:sub>\n                    which was attenuated by NBMI; ( iv) mercury caused loss of intracellular glutathione which was restored by NBMI; and ( v) NBMI and FIPI attenuated mercury- and oxidant-induced cytotoxicity in MAECs. For the first time, this study demonstrated that redox-dependent and PLD-mediated bioactive lipid signaling was involved in mercury-induced vascular EC cytotoxicity which was protected by NBMI and FIPI.\n                  <\/jats:p>","DOI":"10.1177\/1091581811422413","type":"journal-article","created":{"date-parts":[[2011,10,13]],"date-time":"2011-10-13T00:46:18Z","timestamp":1318466778000},"page":"619-638","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["Novel Lipid-Soluble Thiol-Redox Antioxidant and Heavy Metal Chelator,\n                    <i>N<\/i>\n                    ,\n                    <i>N<\/i>\n                    \u2032-bis(2-Mercaptoethyl)Isophthalamide (NBMI) and Phospholipase D-Specific Inhibitor, 5-Fluoro-2-Indolyl Des-Chlorohalopemide (FIPI) Attenuate Mercury-Induced Lipid Signaling Leading to Protection Against Cytotoxicity in Aortic Endothelial Cells"],"prefix":"10.1177","volume":"30","author":[{"given":"Jordan D.","family":"Secor","sequence":"first","affiliation":[{"name":"Lipid Signaling, Lipidomics, and Vasculotoxicity Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Dorothy M. Davis Heart and Lung Research Institute and Division of Pharmacology, Colleges of Medicine and Pharmacy, The Ohio State University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sainath R.","family":"Kotha","sequence":"additional","affiliation":[{"name":"Lipid Signaling, Lipidomics, and Vasculotoxicity Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Dorothy M. Davis Heart and Lung Research Institute and Division of Pharmacology, Colleges of Medicine and Pharmacy, The Ohio State University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis O.","family":"Gurney","sequence":"additional","affiliation":[{"name":"Lipid Signaling, Lipidomics, and Vasculotoxicity Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Dorothy M. Davis Heart and Lung Research Institute and Division of Pharmacology, Colleges of Medicine and Pharmacy, The Ohio State University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rishi B.","family":"Patel","sequence":"additional","affiliation":[{"name":"Lipid Signaling, Lipidomics, and Vasculotoxicity Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Dorothy M. Davis Heart and Lung Research Institute and Division of Pharmacology, Colleges of Medicine and Pharmacy, The Ohio State University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas R.","family":"Kefauver","sequence":"additional","affiliation":[{"name":"Lipid Signaling, Lipidomics, and Vasculotoxicity Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Dorothy M. 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Davis Heart and Lung Research Institute and Division of Pharmacology, Colleges of Medicine and Pharmacy, The Ohio State University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2011,10,12]]},"reference":[{"key":"bibr1-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra022471"},{"key":"bibr2-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp020139"},{"issue":"5","key":"bibr3-1091581811422413","first-page":"439","volume":"26","author":"Mutter J","year":"2005","journal-title":"Neuro Endocrinol Lett"},{"key":"bibr4-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1016\/S0045-6535(01)00122-9"},{"key":"bibr5-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020157"},{"key":"bibr6-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-006-9016-0"},{"key":"bibr7-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1080\/10915810601120509"},{"key":"bibr8-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1080\/10408440490270160"},{"key":"bibr9-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4274(96)03741-1"},{"key":"bibr10-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1017\/S031716710000528X"},{"key":"bibr11-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2003.11.032"},{"issue":"6","key":"bibr12-1091581811422413","first-page":"54","volume":"14","author":"Cave SF","year":"2008","journal-title":"Altern Ther Health Med"},{"key":"bibr13-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfr009"},{"key":"bibr14-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1016\/j.cppeds.2010.07.002"},{"key":"bibr15-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.119-a80b"},{"key":"bibr16-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2004.tb00027.x"},{"key":"bibr17-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1007\/s002449900294"},{"issue":"4","key":"bibr18-1091581811422413","first-page":"401","volume":"38","author":"Kim DS","year":"2005","journal-title":"J Prev Med Public Health"},{"key":"bibr19-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021437"},{"key":"bibr20-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1136\/oem.58.7.461"},{"key":"bibr21-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(87)90185-2"},{"key":"bibr22-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1177\/1091581809338077"},{"key":"bibr23-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.91.4.1487"},{"key":"bibr24-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-009-0199-x"},{"key":"bibr25-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2005.10.019"},{"key":"bibr26-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1089\/ars.1999.1.2-193"},{"key":"bibr27-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-008-9793-6"},{"key":"bibr28-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1016\/0009-2797(78)90146-1"},{"key":"bibr29-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-008-9162-7"},{"key":"bibr30-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1021\/jp101668n"},{"key":"bibr31-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1080\/15376510701380505"},{"key":"bibr32-1091581811422413","doi-asserted-by":"publisher","DOI":"10.2174\/1568026013394831"},{"key":"bibr33-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2007.02.016"},{"key":"bibr34-1091581811422413","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3894(01)00190-X"},{"key":"bibr35-1091581811422413","volume-title":"Novel Multidentate Sulfur Containing Ligands. 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