{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T09:14:06Z","timestamp":1696410846404},"reference-count":42,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2016,6,2]],"date-time":"2016-06-02T00:00:00Z","timestamp":1464825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Kaohsiung Veterans General Hospital Tainan Branch","award":["VHYK104-013"],"award-info":[{"award-number":["VHYK104-013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Biochem &amp; Molecular Tox"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The effect of protriptyline on Ca<jats:sup>2+<\/jats:sup> physiology in human hepatoma is unclear. This study explored the effect of protriptyline on [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> and cytotoxicity in HepG2 human hepatoma cells. Protriptyline (50\u2013150\u00a0\u03bcM) evoked [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> rises. The Ca<jats:sup>2+<\/jats:sup> entry was inhibited by removal of Ca<jats:sup>2+<\/jats:sup>. Protriptyline\u2010induced Ca<jats:sup>2+<\/jats:sup> entry was confirmed by Mn<jats:sup>2+<\/jats:sup>\u2010induced quench of fura\u20102 fluorescence. Except nifedipine, econazole, SKF96365, GF109203X, and phorbol 12\u2010myristate 13 acetate did not inhibit Ca<jats:sup>2+<\/jats:sup> entry. Treatment with the endoplasmic reticulum Ca<jats:sup>2+<\/jats:sup> pump inhibitor 2,5\u2010di\u2010tert\u2010butylhydroquinone (BHQ) inhibited 40% of protriptyline\u2010induced response. Treatment with protriptyline abolished BHQ\u2010induced response. Inhibition of phospholipase C (PLC) suppressed protriptyline\u2010evoked response by 70%. At 20\u201340\u00a0\u03bcM, protriptyline killed cells which was not reversed by the Ca<jats:sup>2+<\/jats:sup> chelator 1,2\u2010bis(2\u2010aminophenoxy)ethane\u2010N,N,N\u2032,N\u2032\u2010tetraacetic acid\u2010acetoxymethyl ester (BAPTA\/AM). Together, in HepG2 cells, protriptyline induced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> rises that involved Ca<jats:sup>2+<\/jats:sup> entry through nifedipine\u2010sensitive Ca<jats:sup>2+<\/jats:sup> channels and PLC\u2010dependent Ca<jats:sup>2+<\/jats:sup> release from endoplasmic reticulum. Protriptyline induced Ca<jats:sup>2+<\/jats:sup>\u2010independent cell death.<\/jats:p>","DOI":"10.1002\/jbt.21820","type":"journal-article","created":{"date-parts":[[2016,6,2]],"date-time":"2016-06-02T08:52:42Z","timestamp":1464857562000},"page":"539-547","source":"Crossref","is-referenced-by-count":0,"title":["Ca<sup>2+<\/sup> Signaling and Cell Death Induced by Protriptyline in HepG2 Human Hepatoma Cells"],"prefix":"10.1002","volume":"30","author":[{"given":"Jue\u2010Long","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Kaohsiung Veterans General Hospital Tainan Branch  Tainan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiang\u2010Ting","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Nursing, Division of Basic Medical Sciences Chang Gung Institute of Technology  Chia\u2010Yi Taiwan"},{"name":"Chronic Diseases and Health Promotion Research Center Chang Gung Institute of Technology  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