Cisplatin-induced apoptosis of DRG neurons involves bax redistribution and cytochrome c release but not fas receptor signaling
Cisplatin-induced apoptosis of DRG neurons involves bax redistribution and cytochrome c release but not fas receptor signaling
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DOI：
10.1006/nbdi.2001.0468
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发表时间：
2002-03-01
影响因子：
6.1
通讯作者：
Windebank, AJ
中科院分区：
文献类型：
--
作者：
McDonald, ES;Windebank, AJ
顺铂在体内外均可引起DRG神经元凋亡，而大剂量的NGF可抑制顺铂引起的DRG神经元凋亡。了解顺铂导致DRG死亡的机制有助于设计接受顺铂治疗的患者的神经元拯救策略。Fas受体/配体相互作用的抑制防止用DNA损伤剂（包括顺铂）处理的某些癌细胞系中的凋亡。我们证明，在一个治疗相关的浓度范围内，缺乏功能性fas受体的小鼠和野生型对照小鼠的杀伤曲线没有差异。然而，顺铂治疗DRG引起细胞溶质bax和细胞色素c的线粒体释放的重新分布。高剂量NGF可抑制Bax的再分布。这首次证明顺铂不通过Fas途径发出死亡信号，但它确实启动了神经元中的线粒体应激途径，并且NGF阻断了bax再分布上游的死亡。(C)2002 Elsevier Science（美国）。
Cisplatin causes apoptosis of DRG neurons in vitro and in vivo that can be prevented by high dose NGF. Design of a neuronal rescue strategy for patients receiving cisplatin will be facilitated by knowledge of the mechanism by which cisplatin causes DRG death. Inhibition of the fas receptor/ligand interaction prevents apoptosis in certain cancer cell lines treated with DNA damaging agents, including cisplatin. We demonstrated that killing curves from mice lacking a functional fas receptor and wild-type controls were not different over a wide range of therapeutically relevant concentrations. However, cisplatin treatment of DRG caused redistribution of cytosolic bax and mitochondrial release of cytochrome c. Bax redistribution was prevented by high dose NGF. This demonstrates for the first time that cisplatin does not signal for death via the fas pathway, but it does initiate the mitochondrial stress pathway in neurons and that NGF blocks death upstream of bax redistribution. (C) 2002 Elsevier Science (USA).