Huang C, Ma W y, Ding M, Bowden G T, Dong Z
The Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.
J Biol Chem. 1997 Oct 31;272(44):27753-7. doi: 10.1074/jbc.272.44.27753.
Sphingomyelinase (SMase) and its product ceramide have recently attracted a great deal of attention because of their possible role in the signal transduction pathway. However, the role of sphingomyelinase in UV-induced c-June N-terminal kinase (JNK) activation is still unclear. Thus, we investigated this issue directly using a genetic SMase-deficient (2 approximately 3% residual acid SMase activity) lymphoblast cell line, MS1418. The results showed that while UV irradiation markedly induces JNK activation in a normal human lymphoblast cell line, JY, it induces only weak JNK activation in MS1418 cells. This difference of JNK response to UV irradiation between these two cell lines was further observed in time course and dose-response studies. In contrast, 12-O-tetradecanoylphorbol-13-acetate-induced JNK activation could be observed in both JY and MS1418 cells. Furthermore, significant JNK activation can be observed in MS1418 cells by exposure of the cells to SMase or C2-ceramide, whereas phospholipase A2 or phospholipase C did not show significant induction of JNK activity, and C2-dihydroceramide and sphingosine induce only much weaker JNK activation in MS1418 cells than that by C2-ceramide. These data demonstrated that SMase plays an essential role in UV-induced JNK activation.
鞘磷脂酶（SMase）及其产物神经酰胺因其在信号转导途径中可能发挥的作用，近来备受关注。然而，鞘磷脂酶在紫外线诱导的c-Jun N端激酶（JNK）激活中的作用仍不清楚。因此，我们使用遗传性鞘磷脂酶缺陷型（残余酸性鞘磷脂酶活性约为2%至3%）淋巴母细胞系MS1418直接研究了这一问题。结果显示，紫外线照射在正常人淋巴母细胞系JY中可显著诱导JNK激活，而在MS1418细胞中仅诱导微弱的JNK激活。在时间进程和剂量反应研究中进一步观察到了这两种细胞系对紫外线照射的JNK反应差异。相比之下，在JY和MS1418细胞中均能观察到12-O-十四烷酰佛波醇-13-乙酸酯诱导的JNK激活。此外，将MS1418细胞暴露于鞘磷脂酶或C2-神经酰胺中可观察到显著的JNK激活，而磷脂酶A2或磷脂酶C未显示出对JNK活性的显著诱导，并且C2-二氢神经酰胺和鞘氨醇在MS1418细胞中诱导的JNK激活比C2-神经酰胺弱得多。这些数据表明，鞘磷脂酶在紫外线诱导的JNK激活中起重要作用。
