Downregulation of the c-MYC target gene, peroxiredoxin III, contributes to arsenic trioxide-induced apoptosis in acute promyelocytic leukemia.
Downregulation of the c-MYC target gene, peroxiredoxin III, contributes to arsenic trioxide-induced apoptosis in acute promyelocytic leukemia.
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DOI：
10.1002/ijc.24341
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发表时间：
2009-07-15
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
--
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Arsenic trioxide (ATO) induces differentiation and apoptosis in acute promyelocytic leukemia (APL). Several reports indicate that in APL cells apoptosis occurs mainly by a mechanism that involves the inhibition of glutathione peroxidase, one of the enzymes that regulates mitochondrial levels of H2O2. Peroxiredoxin (Prx) III, a c-MYC target gene, is also a mitochondria-specific H2O2-scavenger enzyme. We studied here the role of Prx III during ATO-induced apoptosis in APL-derived NB4 cells, since these cells express high levels of Prx III. The protein and mRNA levels of Prx III decreased during ATO-induced apoptosis of NB4 cells. The downregulation of Prx III occurred before reactive oxygen species accumulation, reduction in the mitochondrial membrane potential and apoptosis. Depletion of Prx III enhanced mitochondrial-dependent apoptosis events. In contrast, overexpression of Prx III led to reduced levels of ATO-induced apoptosis. c-MYC was also downregulated in ATO-treated NB4 cells. Furthermore, depletion of c-MYC also reduced the Prx-III expression levels. Finally chromatin immunoprecipitation and luciferase reporter assays confirmed that downregulation of Prx-III was caused by the reduction of c-MYC levels during ATO-induced apoptosis of NB4 cells. These findings demonstrate a novel apoptotic-response pathway whereby downregulation of Prx-III potentiates ATO-induced apoptosis in APL cells.
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DOI：
10.1073/pnas.0306687101
发表时间：
2004-03-30
影响因子：
11.1
作者：
Chou, WC;Jie, CF;Dang, CV
通讯作者：
Dang, CV
影响因子：
4.8
作者：
Joe, YeonSoo;Jeong, Jae-Hoon;Kim, Myung K.
通讯作者：
Kim, Myung K.
影响因子：
4.8
作者：
Cheema, SK;Mishra, SK;Lopez-Berestein, G
通讯作者：
Lopez-Berestein, G
影响因子：
4
作者：
Floryk, D;Houstek, J
通讯作者：
Houstek, J
影响因子：
11.4
作者：
Cavigelli, M;Li, WW;Karin, M
通讯作者：
Karin, M