The role of mitochondrial targeting in arsenic trioxide-induced apoptosis in myeloid cell lines |
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Authors: | Körper Sixten Nolte Florian Thiel Eckhard Schrezenmeier Hubert Rojewski Markus T |
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Institution: | Institut für klinische Transfusionsmedizin und Immungenetik Ulm und Abtl. Transfusionsmedizin der Universit?t Ulm, Helmholtz-Strasse 10, D-89081 Ulm, Germany. sixten.koerper@medizin.uni-ulm.de |
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Abstract: | Data regarding the role of mitochondria in arsenic trioxide (As2O3)-induced apoptosis are controversial. We investigated the contribution of caspases and mitochondrial depolarization to As2O3-induced apoptosis in the myeloid cell lines NB-4, HL-60 and U-937. Caspase inhibition reduced the amount of cells with As2O3 (20 micromol/l)-induced mitochondrial depolarization by about 50% in all cell lines. As2O3 also induced dose-dependent phosphatidylserine exposure in cells without depolarized mitochondria. We conclude that caspase activation is of similar importance in As2O3-induced apoptosis in myeloid cell lines as direct mitochondrial targeting and mitochondria are not necessary for caspase activation downstream of mitochondria. |
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Keywords: | arsenic trioxide mitochondria caspases apoptosis JC-1 |
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