Hydrogen peroxide activation of ERK5 confers resistance to Jurkat cells against apoptosis induced by the extrinsic pathway.
Hydrogen peroxide activation of ERK5 confers resistance to Jurkat cells against apoptosis induced by the extrinsic pathway.
复制标题
过氧化氢激活 ERK5 赋予 Jurkat 细胞抵抗外源途径诱导的细胞凋亡的能力。
DOI：
10.1016/j.bbrc.2014.01.058
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发表时间：
2014
影响因子：
3.1
通讯作者：
Yang,Jay
中科院分区：
文献类型：
--
作者：
Suzuki,Takeshi;Yang,Jay
包括过氧化氢（H2 O2）在内的活性氧（ROS）在白血病细胞中表现出促生存和促死亡信号。本实验观察了外源性H_2O_2对Fas配体（FasL）诱导的Jurkat细胞凋亡的影响。H2 O2在FasL刺激前（预处理）和刺激后（处理）通过激活EKR 5减弱早期凋亡。H2 O2增加了激活的caspase-8螯合在线粒体中，从而减少细胞死亡通过外源性凋亡途径。此外，蛋白酪氨酸磷酸酶的抑制可能解释了对H2 O2的后调节要求。考虑到用于治疗急性淋巴细胞白血病的化学治疗剂被认为部分地通过ROS的产生起作用，ERK 5途径的同时抑制可以消除ROS引发的促存活信号传导以增强细胞杀伤。
Reactive oxygen species (ROS) including hydrogen peroxide (H2O2) exhibit both pro-survival and pro-death signaling in leukemic cells. We examined the effect of exogenous H2O2on Fas ligand (FasL) -induced apoptosis in Jurkat cells. H2O2applied prior to (pre-conditioning) and during (post-conditioning) FasL stimulation attenuated early apoptosis through activation of EKR5. H2O2increased the activated caspase-8 sequestered in the mitochondria thereby decreasing cell death through the extrinsic apoptotic pathway. In addition, inhibition of a protein tyrosine phosphatase likely explains the post-conditioning requirement for H2O2. Given that chemotherapeutic agents used for the treatment of acute lymphoblastic leukemia are thought to work partly through production of ROS, a simultaneous inhibition of the ERK5 pathway may abrogate the ROS-initiated pro-survival signaling for an enhanced cell kill.