{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:52:54Z","timestamp":1790232774682,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,10,13]],"date-time":"2009-10-13T00:00:00Z","timestamp":1255392000000},"content-version":"vor","delay-in-days":42,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Biochem &amp; Molecular Tox"],"published-print":{"date-parts":[[2009,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Oxysterols, such as 7\u03b2\u2010hydroxy\u2010cholesterol (7\u03b2\u2010OH) and cholesterol\u20105\u03b2,6\u03b2\u2010epoxide (\u03b2\u2010epoxide), may have a central role in promoting atherogenesis. This is thought to be predominantly due to their ability to induce apoptosis in cells of the vascular wall and in monocytes\/macrophages. Although there has been extensive research regarding the mechanisms through which oxysterols induce apoptosis, much remains to be clarified. Given that experimental evidence has long associated alterations of calcium (Ca<jats:sup>2+<\/jats:sup>) homeostasis to apoptotic cell death, the aim of the present study was to determine the influence of intracellular Ca<jats:sup>2+<\/jats:sup> changes on apoptosis induced by 7\u03b2\u2010OH and \u03b2\u2010epoxide. Ca<jats:sup>2+<\/jats:sup> responses in differentiated U937 cells were assessed by epifluorescence video microscopy, using the ratiometric dye fura\u20102. Over 15\u2010min exposure of differentiated U937 cells to 30 \u03bcM of 7\u03b2\u2010OH induced a slow but significant rise in fura\u20102 ratio. The Ca<jats:sup>2+<\/jats:sup> channel blocker nifedipine and the chelating agent EGTA blocked the increase in cytoplasmic Ca<jats:sup>2+<\/jats:sup>. Moreover, dihydropyridine (DHP) binding sites identified with BODIPY\u2010FLX\u2010DHP were blocked following pretreatment with nifedipine, indicating that the influx of Ca<jats:sup>2+<\/jats:sup> occurred through L\u2010type channels. However, following long\u2010term incubation with 7\u03b2\u2010OH, elevated levels of cytoplasmic Ca<jats:sup>2+<\/jats:sup> were not maintained and nifedipine did not provide protection against apoptotic cell death. Our results indicate that the increase in Ca<jats:sup>2+<\/jats:sup> may be an initial trigger of 7\u03b2\u2010OH\u2013induced apoptosis, but following chronic exposure to the oxysterol, the influence of Ca<jats:sup>2+<\/jats:sup> on apoptotic cell death appears to be less significant. In contrast, Ca<jats:sup>2+<\/jats:sup> did not appear to be involved in \u03b2\u2010epoxide\u2013induced apoptosis. \u00a9 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:324\u2013332, 2009; Published online in Wiley InterScience (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.interscience.wiley.com\">www.interscience.wiley.com<\/jats:ext-link>). 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