Dual signaling of the Fas receptor: initiation of both apoptotic and necrotic cell death pathways.
Dual signaling of the Fas receptor: initiation of both apoptotic and necrotic cell death pathways.
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FAS受体的双重信号传导：凋亡和坏死细胞死亡途径的启动。
DOI：
10.1084/jem.188.5.919
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发表时间：
1998-09-07
期刊：
影响因子：
--
通讯作者：
Vandenabeele P
中科院分区：
文献类型：
--
作者：
Vercammen D;Brouckaert G;Denecker G;Van de Craen M;Declercq W;Fiers W;Vandenabeele P
用人Fas（APO-1/CD 95）受体转染小鼠L929纤维肉瘤细胞，并评估各种半胱天冬酶在Fas介导的细胞死亡中的作用。Western分析显示蛋白酶原-3和-7的蛋白水解活化。乙酰基-Tyr-Val-Ala-Asp-氯甲基酮和苄氧羰基-Asp（OMe）-Glu（OMe）-Val-Asp（OMe）-氟甲基酮，分别是caspase-1和caspase-3样蛋白酶的四肽抑制剂，不能阻断Fas诱导的细胞凋亡。出乎意料的是，广谱半胱天冬酶抑制剂苄氧基羰基-Val-Ala-Asp（OMe）-氟甲基酮和苄氧基羰基-Asp（OMe）-氟甲基酮使细胞对Fas介导的细胞死亡更加敏感，如孵育18小时后所测量的。然而，当显微镜下观察该过程时，很明显，抗Fas诱导的Fas转染的L929细胞凋亡在前3小时内被阻断，随后细胞因坏死而死亡。在肿瘤坏死因子（TNF）诱导的坏死，Fas治疗导致活性氧自由基的积累，和Fas介导的坏死抑制氧自由基清除剂丁基羟基茴香醚。然而，与TNF相反，抗Fas在这些坏死条件下不激活核因子κB。这些结果表明，存在两种不同的途径起源于Fas受体，一个迅速导致细胞凋亡，并且，如果这种细胞凋亡途径被半胱天冬酶抑制剂阻断，第二个指导细胞坏死，并涉及氧自由基的产生。
Murine L929 fibrosarcoma cells were transfected with the human Fas (APO-1/CD95) receptor, and the role of various caspases in Fas-mediated cell death was assessed. Proteolytic activation of procaspase-3 and -7 was shown by Western analysis. Acetyl-Tyr-Val-Ala-Asp-chloromethylketone and benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethylketone, tetrapeptide inhibitors of caspase-1– and caspase-3–like proteases, respectively, failed to block Fas-induced apoptosis. Unexpectedly, the broad-spectrum caspase inhibitors benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone and benzyloxycarbonyl-Asp(OMe)-fluoromethylketone rendered the cells even more sensitive to Fas-mediated cell death, as measured after 18 h incubation. However, when the process was followed microscopically, it became clear that anti-Fas–induced apoptosis of Fas-transfected L929 cells was blocked during the first 3 h, and subsequently the cells died by necrosis. As in tumor necrosis factor (TNF)-induced necrosis, Fas treatment led to accumulation of reactive oxygen radicals, and Fas-mediated necrosis was inhibited by the oxygen radical scavenger butylated hydroxyanisole. However, in contrast to TNF, anti-Fas did not activate the nuclear factor κB under these necrotic conditions. These results demonstrate the existence of two different pathways originating from the Fas receptor, one rapidly leading to apoptosis, and, if this apoptotic pathway is blocked by caspase inhibitors, a second directing the cells to necrosis and involving oxygen radical production.
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影响因子：
30.8
作者：
Goldberg, YP;Nicholson, DW;Hayden, MR
通讯作者：
Hayden, MR
DOI：
10.1073/pnas.94.5.2007
发表时间：
1997-03-04
影响因子：
11.1
作者：
Hara, H;Friedlander, RM;Moskowitz, MA
通讯作者：
Moskowitz, MA
影响因子：
64.5
作者：
HSU, HL;XIONG, J;GOEDDEL, DV
通讯作者：
GOEDDEL, DV
影响因子：
64.5
作者：
Boldin, MP;Goncharov, TM;Wallach, D
通讯作者：
Wallach, D
影响因子：
56.9
作者：
Chinnaiyan, AM;ORourke, K;Dixit, VM
通讯作者：
Dixit, VM