{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:01:43Z","timestamp":1791291703000,"version":"4.1.0"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,5,1]]},"abstract":"<jats:p>In cyanide-induced apoptosis, an increase in cytosolic free Ca2+ and generation of reactive oxygen species are initiation stimuli for apoptotic cell death. Previous studies have shown that cyanide-stimulated translocation of Bax (Bcl-associated X protein) to mitochondria is linked with release of cytochrome c and subsequent activation of a caspase cascade [Shou, Li, Prabhakaran, Borowitz and Isom (2003) Toxicol. Sci. 75, 99\u2013107]. In the present study, the relationship of the cyanide-induced increase in cytosolic free Ca2+ to activation of Bad (Bcl-2\/Bcl-XL-antagonist, causing cell death) was determined in cortical cells. Bad is a Ca2+-sensitive pro-apoptotic Bcl-2 protein, which on activation translocates from cytosol to mitochondria to initiate cytochrome c release. In cultured primary cortical cells, cyanide produced a concentration- and time-dependent translocation of Bad from cytosol to mitochondria. Translocation occurred early in the apoptotic response, since mitochondrial Bad was detected within 1 h of cyanide treatment. Mitochondrial levels of the protein continued to increase up to 12 h post-cyanide exposure. Concurrent with Bad translocation, a Ca2+-sensitive increase in cellular calcineurin activity was observed. Increased cytosolic Ca2+ and calcineurin activation stimulated Bad translocation since BAPTA [bis-(o-aminophenoxy)ethane-N,N,N\u00b4,N\u00b4-tetra-acetic acid], an intracellular Ca2+ chelator, and cyclosporin A, a calcineurin inhibitor, significantly reduced translocation. BAPTA also blocked release of cytochrome c from mitochondria as well as apoptosis. Furthermore, treatment of cells with the calcineurin inhibitors cyclosporin A or FK506 blocked the apoptotic response, linking calcineurin activation and the subsequent translocation of Bad to cell death. These observations show that by inducing a rapid increase in cytosolic free Ca2+, cyanide can partially initiate the apoptotic cascade through a calcineurin-mediated translocation of Bad to mitochondria.<\/jats:p>","DOI":"10.1042\/bj20031107","type":"journal-article","created":{"date-parts":[[2004,4,26]],"date-time":"2004-04-26T15:26:43Z","timestamp":1082993203000},"page":"805-813","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Calcineurin-mediated Bad translocation regulates cyanide-induced neuronal apoptosis"],"prefix":"10.1042","volume":"379","author":[{"given":"Yan","family":"SHOU","sequence":"first","affiliation":[{"name":"Neurotoxicology Laboratory, Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907-2091, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"LI","sequence":"additional","affiliation":[{"name":"Neurotoxicology Laboratory, Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907-2091, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnan","family":"PRABHAKARAN","sequence":"additional","affiliation":[{"name":"Neurotoxicology Laboratory, Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907-2091, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L.","family":"BOROWITZ","sequence":"additional","affiliation":[{"name":"Neurotoxicology Laboratory, Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907-2091, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary E.","family":"ISOM","sequence":"additional","affiliation":[{"name":"Neurotoxicology Laboratory, Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907-2091, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/379\/3\/805\/713496\/bj3790805.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/379\/3\/805\/713496\/bj3790805.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T12:58:55Z","timestamp":1637585935000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/379\/3\/805\/41436\/Calcineurin-mediated-Bad-translocation-regulates"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,5,1]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2004,5,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bj20031107","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,5,1]]}}}