Charruyer Alexandra, Grazide Solène, Bezombes Christine, Müller Sabina, Laurent Guy, Jaffrézou Jean-Pierre
INSERM U563, Centre de Physiopathologie de Toulouse-Purpan, Centre Hospitalier Universitaire Purpan, 31024 Toulouse, France.
J Biol Chem. 2005 May 13;280(19):19196-204. doi: 10.1074/jbc.M412867200. Epub 2005 Mar 11.
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.
在哺乳动物细胞中,紫外线诱导信号的启动在很大程度上被认为是在DNA损伤之后发生的。几项研究还将神经酰胺(CER),一种脂质第二信使,描述为介导紫外线诱导的c-Jun氨基末端激酶(JNK)激活和细胞死亡的主要因素。本文证明,U937细胞经紫外线-C照射后,会导致一种不依赖锌的酸性鞘磷脂酶激活并易位,从而导致CER在脂筏微结构域中积累。这些富含CER的脂筏聚集并在JNK激活中发挥功能作用。紫外线-C光也能诱导人血小板中CER的产生以及酸性鞘磷脂酶和JNK的外化,这一观察结果最终排除了DNA损伤产生的核信号参与在质膜上产生的紫外线光反应启动的可能性。