Stimulation of ultraviolet-induced apoptosis of human fibroblast UVr-1 cells by tyrosine kinase inhibitors
Stimulation of ultraviolet-induced apoptosis of human fibroblast UVr-1 cells by tyrosine kinase inhibitors
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DOI：
10.1016/s0014-5793(99)00057-5
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发表时间：
1999-02-12
期刊：
影响因子：
3.5
通讯作者：
Suzuki, N
中科院分区：
文献类型：
--
作者：
Hiwasa, T;Arase, Y;Suzuki, N
Damnacanthal 是一种从 Morinda citrifolia 根中分离出来的蒽醌化合物，据报道对酪氨酸激酶（如 Lck、Src、Lyn 和 EGF 受体）具有有效的抑制活性。在本研究中，我们研究了damacanthal 对紫外线诱导的抗紫外线人类UVr-1 细胞凋亡的影响。当在紫外线照射之前用damnacanthal处理细胞时，与单独紫外线照射的情况相比，DNA断裂更加明显。其他酪氨酸激酶抑制剂，除草霉素 A 和金雀异黄素，也对紫外线诱导的细胞凋亡产生类似的作用，但丝氨酸/苏氨酸激酶抑制剂 K252a、星形孢菌素和 GF109203X 在较小程度上抑制了紫外线诱导的 DNA 裂解。免疫印迹分析表明，用damacanthal预处理后进行紫外线照射，增加了磷酸化细胞外信号调节激酶和应激激活蛋白激酶的水平，而其他酪氨酸激酶抑制剂并没有增加细胞外信号调节激酶的磷酸化，而是刺激了应激激活蛋白激酶的磷酸化，因此，紫外线诱导的磷酸化细胞外信号调节激酶和应激激活蛋白激酶同时增加。 damnacanthal 可能与damnacanthal 对紫外线诱导的细胞凋亡的刺激作用有关。 (C) 1999 年欧洲生化学会联合会。
Damnacanthal is an anthraquinone compound isolated from the root of Morinda citrifolia and was reported to have a potent inhibitory activity towards tyrosine kinases such as Lck, Src, Lyn and EGF receptor. In the present study, we have examined the effects of damnacanthal on ultraviolet ray-induced apoptosis in ultraviolet-resistant human UVr-1 cells. When the cells were treated with damnacanthal prior to ultraviolet irradiation, DNA fragmentation was more pronounced as compared to the case of ultraviolet irradiation alone. The other tyrosine kinase inhibitors, herbimycin A and genistein, also caused similar effects on ultraviolet-induced apoptosis but to a lesser extent, Serine/threonine kinase inhibitors, K252a, staurosporine and GF109203X, rather suppressed the ultraviolet-induced DNA cleavage. Immunoblot analysis showed that pretreatment with damnacanthal followed by ultraviolet irradiation increased the levels of phosphorylated extracellular signal-regulated kinases and stress-activated protein kinases, However, the other tyrosine kinase inhibitors did not increase the phosphorylation of extracellular signal-regulated kinases but stimulated phosphorylation of stress-activated protein kinases, Consequently, the ultraviolet-induced concurrent increase in both phosphorylated extracellular signal-regulated kinases and stress-activated protein kinases after pretreatment with damnacanthal might be characteristically related to the stimulatory effect of damnacanthal on ultraviolet-induced apoptosis. (C) 1999 Federation of European Biochemical Societies.