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The role of mitochondrial targeting in arsenic trioxide‐induced apoptosis in myeloid cell lines
Author(s) -
Körper Sixten,
Nolte Florian,
Thiel Eckhard,
Schrezenmeier Hubert,
Rojewski Markus T.
Publication year - 2004
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2003.04742.x
Subject(s) - arsenic trioxide , mitochondrion , apoptosis , microbiology and biotechnology , caspase , mitochondrial apoptosis induced channel , depolarization , cell culture , phosphatidylserine , intrinsic apoptosis , chemistry , caspase 9 , programmed cell death , cytochrome c , cell , biology , biochemistry , biophysics , membrane , genetics , phospholipid
Summary Data regarding the role of mitochondria in arsenic trioxide (As 2 O 3 )‐induced apoptosis are controversial. We investigated the contribution of caspases and mitochondrial depolarization to As 2 O 3 ‐induced apoptosis in the myeloid cell lines NB‐4, HL‐60 and U‐937. Caspase inhibition reduced the amount of cells with As 2 O 3 (20  μ mol/l)‐induced mitochondrial depolarization by about 50% in all cell lines. As 2 O 3 also induced dose‐dependent phosphatidylserine exposure in cells without depolarized mitochondria. We conclude that caspase activation is of similar importance in As 2 O 3 ‐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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