A critical role of neural-specific JNK3 for ischemic apoptosis
A critical role of neural-specific JNK3 for ischemic apoptosis
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DOI：
10.1073/pnas.2336254100
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发表时间：
2003-12-09
影响因子：
11.1
通讯作者：
Rakic, P
中科院分区：
文献类型：
--
作者：
Kuan, CY;Whitmarsh, AJ;Rakic, P
C-Jun氨基末端激酶(JNK)信号转导通路在应激诱导的细胞凋亡中起重要作用，但JNK及其异构体(JNK1、JNK2、JNK3)在脑缺血中的作用尚不清楚。在这里，我们证明了JNK1是大脑中基础JNK活性高水平的主要亚型。相反，靶向缺失JNK3不仅可以降低应激诱导的JNK活性，还可以保护小鼠脑缺血缺氧后的脑损伤。JNK3介导的细胞凋亡的下游机制可能包括诱导Bim、Fas和线粒体释放细胞色素c。这些结果表明JNK3可能是卒中神经保护治疗的潜在靶点。
c-Jun N-terminal kinase (JNK) signaling is an important contributor to stress-induced apoptosis, but it is unclear whether JNK and its isoforms (JNK1, JNK2, and JNK3) have distinct roles in cerebral ischemia. Here we show that JNK1 is the major isoform responsible for the high level of basal JNK activity in the brain. In contrast, targeted deletion of Jnk3 not only reduces the stress-induced JNK activity, but also protects mice from brain injury after cerebral ischemia-hypoxia. The downstream mechanism of JNK3-mediated apoptosis may include the induction of Bim, and Fas and the mitochondrial release of cytochrome c. These results suggest that JNK3 is a potential target for neuroprotection therapies in stroke.