{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:29:39Z","timestamp":1787066979468,"version":"build-2736575974"},"reference-count":52,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context:<\/jats:title>\n                    <jats:p>Amiodarone (AMIO) is one of the most effective antiarrhythmic drugs available; however, its use is limited by a serious side effect profile, including thyroiditis. The mechanisms underlying AMIO thyroid toxicity have been elusive; thus, identification of novel approaches in order to prevent thyroiditis is essential in patients treated with AMIO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Our aim was to evaluate whether AMIO treatment could induce endoplasmic reticulum (ER) stress in human thyroid cells and the possible implications of this effect in AMIO-induced destructive thyroiditis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Here we report that AMIO, but not iodine, significantly induced the expression of ER stress markers including Ig heavy chain-binding protein (BiP), phosphoeukaryotic translation initiation factor 2\u03b1 (eIF2\u03b1), CCAAT\/enhancer-binding protein homologous protein (CHOP) and spliced X-box binding protein-1 (XBP-1) in human thyroid ML-1 cells and human primary thyrocytes. In both experimental systems AMIO down-regulated thyroglobulin (Tg) protein but had little effect on Tg mRNA levels, suggesting a mechanism involving Tg protein degradation. Indeed, pretreatment with the specific proteasome inhibitor MG132 reversed AMIO-induced down-regulation of Tg protein levels, confirming a proteasome-dependent degradation of Tg protein. Corroborating our findings, pretreatment of ML-1 cells and human primary thyrocytes with the chemical chaperone 4-phenylbutyric acid completely prevented the effect of AMIO on both ER stress induction and Tg down-regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>We identified ER stress as a novel mechanism contributing to AMIO-induced destructive thyroiditis. Our data establish that AMIO-induced ER stress impairs Tg expression via proteasome activation, providing a valuable therapeutic avenue for the treatment of AMIO-induced destructive thyroiditis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/jc.2014-2745","type":"journal-article","created":{"date-parts":[[2014,10,8]],"date-time":"2014-10-08T12:25:08Z","timestamp":1412771108000},"page":"E1-E10","source":"Crossref","is-referenced-by-count":30,"title":["Endoplasmic Reticulum Stress as a Novel Mechanism in Amiodarone-Induced Destructive Thyroiditis"],"prefix":"10.1210","volume":"100","author":[{"given":"Angela","family":"Lombardi","sequence":"first","affiliation":[{"name":"Division of Endocrinology (A.L., K.E.F., Y.T.), New York 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"William Barlow","family":"Inabnet","sequence":"additional","affiliation":[{"name":"Department of Surgery (W.B.I., R.O.), Icahn School of Medicine at Mt Sinai, New York, New York 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall","family":"Owen","sequence":"additional","affiliation":[{"name":"Department of Surgery (W.B.I., R.O.), Icahn School of Medicine at Mt Sinai, New York, New York 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn Ellen","family":"Farenholtz","sequence":"additional","affiliation":[{"name":"Division of Endocrinology (A.L., K.E.F., Y.T.), New York 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaron","family":"Tomer","sequence":"additional","affiliation":[{"name":"Division of Endocrinology (A.L., K.E.F., Y.T.), New York 10029"},{"name":"James J. 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