Inhibition of ultraviolet B-induced activator protein-1 (AP-1) activity by aspirin in AP-1-luciferase transgenic mice
Inhibition of ultraviolet B-induced activator protein-1 (AP-1) activity by aspirin in AP-1-luciferase transgenic mice
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DOI：
10.1074/jbc.272.42.26325
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发表时间：
1997-10-17
影响因子：
4.8
通讯作者：
Dong, ZG
中科院分区：
文献类型：
--
作者：
Huang, CS;Ma, WY;Dong, ZG
阿司匹林是一种很有前途的癌症化学预防剂。为了研究阿司匹林作为UV诱导的人皮肤癌化学预防剂的可行性，我们研究了阿司匹林对UVB诱导的激活蛋白-1（AP-1）活性的影响。在JB 6细胞培养体系中，阿司匹林或水杨酸钠（SA）以剂量依赖方式抑制UVB诱导的AP-1活性;这种抑制作用只发生在UVB照射前用阿司匹林或SA预处理的细胞中，而在UVB照射后用阿司匹林或SA处理的细胞中不发生。此外，这些对UVB诱导的AP-1活性的抑制作用似乎是通过阻断MAP激酶家族成员的激活来介导的，包括细胞外信号调节蛋白激酶、c-Jun N-末端激酶和p38，而不是由于阿司匹林吸收UVB光。在AP-1-荧光素酶转基因小鼠的皮肤中，UVB照射诱导AP-1活性迅速增加，用阿司匹林预处理小鼠皮肤可明显阻断UVB诱导的AP-1反式激活。这些数据首次证明阿司匹林和SA是UVB诱导的信号转导的抑制剂，因此可用作皮肤癌的化学预防剂。
Aspirin is under consideration as a promising chemopreventative agent for human cancers, To study the use fulness of aspirin as a chemopreventative agent for UV-induced human skin cancer, we investigated the effect of aspirin on UVB induced activator protein-1 (AP-1) activity, In the JB6 cell culture system, aspirin or sodium salicylate (SA) inhibited UVB-induced AP-1 activity in a dose-dependent manner; this inhibitory effect occurred only in cells pretreated with aspirin or SA before UVB irradiation but not cells treated with aspirin or SA after UVB irradiation. Furthermore, these inhibitory effects on UVB-induced AP-1 activity appeared to be mediated through blocking of activation of MAP kinase family members, including extracellular signal-regulated protein kinases, c-Jun N-terminal kinases, and p38, It was not due to absorption of UVB light by aspirin, In the skin of AP-l-luciferase transgenic mice, UVB irradiation induced a rapid increase in AP-1 activity, which reached the peak at 48 h post-UVB irradiation, The topical pretreatment of mouse skin with aspirin markedly blocked the UVB induced AP-1 transactivation in vivo, These data provide the first evidence that aspirin and SA are inhibitors of W-induced signal transduction and thus could be used as a chemopreventative agent for skin cancer.