UV-C light induces raft-associated acid sphingomyelinase and JNK activation and translocation independently on a nuclear signal
UV-C light induces raft-associated acid sphingomyelinase and JNK activation and translocation independently on a nuclear signal
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DOI：
10.1074/jbc.m412867200
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发表时间：
2005-05-13
影响因子：
4.8
通讯作者：
Jaffrezou, JP
中科院分区：
文献类型：
--
作者：
Charruyer, A;Grazide, S;Jaffrezou, JP
哺乳动物细胞中UV光诱导的信号传导的起始在很大程度上被认为是继DNA损伤之后。一些研究还描述了神经酰胺（CER），脂质第二信使，作为介导UV光诱导的c-Jun N-末端激酶（JNK）激活和细胞死亡的主要贡献者。它在这里表明，UV-C光照射的U937细胞的结果在激活和易位的Zn 2 +-非依赖性酸性鞘磷脂酶，导致CER的积累筏微域。这些富含CER的筏聚集并在JNK激活中发挥功能性作用。UV-C光也诱导CER生成和人血小板中酸性鞘磷脂酶和JNK的外化的观察结果最终排除了由DNA损伤产生的核信号参与启动UV光响应，其在质膜处产生。
The initiation of UV light-induced signaling in mammalian cells is largely considered to be subsequent to DNA damage. Several studies have also described ceramide (CER), a lipid second messenger, as a major contributor in mediating UV light-induced c-Jun N-terminal kinase (JNK) activation and cell death. It is demonstrated here that UV-C light irradiation of U937 cells results in the activation and translocation of a Zn2+-independent acid sphingomyelinase, leading to CER accumulation in raft microdomains. These CER-enriched rafts aggregate and play a functional role in JNK activation. The observation that UV-C light also induced CER generation and the externalization of acid sphingomyelinase and JNK in human platelets conclusively rules out the involvement of a nuclear signal generated by DNA damage in the initiation of a UV light response, which is generated at the plasma membrane.