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Fehlberg, Sebastian; Gregel, Cornelia M; Göke, Alexandra; Göke, Rüdiger

Bisphenol A diglycidyl ether‐induced apoptosis involves Bax/Bid‐dependent mitochondrial release of apoptosis‐inducing factor (AIF), cytochrome c and Smac/DIABLO

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  • Media type: E-Article
  • Title: Bisphenol A diglycidyl ether‐induced apoptosis involves Bax/Bid‐dependent mitochondrial release of apoptosis‐inducing factor (AIF), cytochrome c and Smac/DIABLO
  • Contributor: Fehlberg, Sebastian; Gregel, Cornelia M; Göke, Alexandra; Göke, Rüdiger
  • imprint: Wiley, 2003
  • Published in: British Journal of Pharmacology
  • Language: English
  • DOI: 10.1038/sj.bjp.0705275
  • ISSN: 0007-1188; 1476-5381
  • Keywords: Pharmacology
  • Origination:
  • Footnote:
  • Description: <jats:p> <jats:list list-type="explicit-label"> <jats:list-item><jats:p>Bisphenol A diglycidyl ether (BADGE) is a peroxisome proliferator‐activated receptor‐<jats:italic>γ</jats:italic> (PPAR‐<jats:italic>γ</jats:italic>) antagonist, which is able to induce apoptosis in tumor cells independently of PPAR‐<jats:italic>γ</jats:italic> in caspase‐dependent and ‐independent manners. Additionally, BADGE promotes TRAIL‐induced apoptosis.</jats:p></jats:list-item> <jats:list-item><jats:p>We report that BADGE activates via Bax and caspases‐2 and ‐8 both the intrinsic and extrinsic apoptotic pathways using Bid as a shunt.</jats:p></jats:list-item> <jats:list-item><jats:p>BADGE stimulates the mitochondrial release of apoptosis‐inducing factor (AIF), cytochrome <jats:italic>c</jats:italic> and second mitochondria‐derived activator of caspase/direct IAP‐binding protein with low pl (Smac/DIABLO). The release of cytochrome <jats:italic>c</jats:italic> could not be blocked by inhibitors of caspases‐3, ‐8 and ‐9 indicating that BADGE acts upstream of caspases‐3 and ‐9 and does not involve caspase‐8 to release cytochrome <jats:italic>c</jats:italic>.</jats:p></jats:list-item> <jats:list-item><jats:p>While the caspase‐independent apoptotic effect might be mediated by AIF, the sensitizing effect of BADGE against other apoptotic substances is most likely mediated by the X‐linked inhibitor of apoptosis inhibitor Smac/DIABLO.</jats:p></jats:list-item> <jats:list-item><jats:p>Our data suggest that BADGE or BADGE derivatives could represent promising substances for the treatment of neoplasms improving the antitumoral activity of TRAIL.</jats:p></jats:list-item> </jats:list> </jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic> (2003) <jats:bold>139</jats:bold>, 495–500. doi:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1038/sj.bjp.0705275">10.1038/sj.bjp.0705275</jats:ext-link></jats:p>
  • Access State: Open Access