A BAX/BAK and cyclophilin D-independent intrinsic apoptosis pathway.
A BAX/BAK and cyclophilin D-independent intrinsic apoptosis pathway.
复制标题
BAX/BAK和环磷脂D独立的内在凋亡途径。
DOI：
10.1371/journal.pone.0037782
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hetz C
中科院分区：
文献类型：
--
作者：
Zamorano S;Rojas-Rivera D;Lisbona F;Parra V;Court FA;Villegas R;Cheng EH;Korsmeyer SJ;Lavandero S;Hetz C
大多数内在死亡信号汇聚成线粒体处的促凋亡BCL-2家族成员BAX和巴克的活化，导致细胞色素c的释放和线粒体活化。慢性内质网（ER）应激通过上调促凋亡BH 3-only蛋白亚组，激活线粒体中的BAX和巴克，导致细胞凋亡。在这里，我们提供的证据表明，BAX和巴克双缺陷（DKO）细胞对ER应激的完全抗性通过刺激结合轻度血清戒断而恢复。在这些条件下的细胞死亡的特征在于经典的凋亡标志物，半胱天冬酶-9激活，细胞色素c的释放的外观，并通过敲低半胱天冬酶-9抑制，但不敏感BCL-XL过表达。类似地，BIM和BIA双缺陷细胞对ER应激的抗性通过轻度血清撤回而恢复。令人惊讶的是，BAX/BAK非依赖性细胞死亡不需要亲环素D（CypD）表达，亲环素D是线粒体渗透性转换孔的重要调节剂。我们的研究结果表明，存在一个替代的内在凋亡途径出现的ER和线粒体之间的串扰。
Most intrinsic death signals converge into the activation of pro-apoptotic BCL-2 family members BAX and BAK at the mitochondria, resulting in the release of cytochrome c and apoptosome activation. Chronic endoplasmic reticulum (ER) stress leads to apoptosis through the upregulation of a subset of pro-apoptotic BH3-only proteins, activating BAX and BAK at the mitochondria. Here we provide evidence indicating that the full resistance of BAX and BAK double deficient (DKO) cells to ER stress is reverted by stimulation in combination with mild serum withdrawal. Cell death under these conditions was characterized by the appearance of classical apoptosis markers, caspase-9 activation, release of cytochrome c, and was inhibited by knocking down caspase-9, but insensitive to BCL-XL overexpression. Similarly, the resistance of BIM and PUMA double deficient cells to ER stress was reverted by mild serum withdrawal. Surprisingly, BAX/BAK-independent cell death did not require Cyclophilin D (CypD) expression, an important regulator of the mitochondrial permeability transition pore. Our results suggest the existence of an alternative intrinsic apoptosis pathway emerging from a cross talk between the ER and the mitochondria.
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影响因子：
16
作者：
Harding, HP;Zhang, YH;Ron, D
通讯作者：
Ron, D
影响因子：
4
作者：
Kim, AJ;Shi, YY;Werstuck, GH
通讯作者：
Werstuck, GH
DOI：
10.1523/jneurosci.4065-10.2011
发表时间：
2011-01-19
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Barrientos SA;Martinez NW;Yoo S;Jara JS;Zamorano S;Hetz C;Twiss JL;Alvarez J;Court FA
通讯作者：
Court FA
影响因子：
3.4
作者：
Costes, SV;Daelemans, D;Lockett, S
通讯作者：
Lockett, S
影响因子：
64.8
作者：
Baines, CP;Kaiser, RA;Molkentin, JD
通讯作者：
Molkentin, JD