Acetylcholinesterase expression mediated by c-Jun-NH2-terminal kinase pathway during anticancer drug-induced apoptosis
Acetylcholinesterase expression mediated by c-Jun-NH2-terminal kinase pathway during anticancer drug-induced apoptosis
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抗癌药物诱导细胞凋亡过程中 c-Jun-NH2 末端激酶通路介导的乙酰胆碱酯酶表达
DOI：
10.1038/sj.onc.1209686
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发表时间：
2006-11-09
期刊：
影响因子：
8
通讯作者：
Zhu, X-F
中科院分区：
文献类型：
--
作者：
Deng, R.;Li, W.;Zhu, X-F
研究表明，乙酰胆碱酯酶（AChE）在细胞凋亡过程中被诱导表达，AChE的反义寡核苷酸和siRNA可能在多种细胞类型中阻止细胞凋亡。然而，乙酰胆碱酯酶上调的机制仍然难以捉摸。我们在这里证明了c-Jun nh2末端激酶（JNK）可以介导AChE的表达。在本研究中，通过Annexin V染色、caspase-3的裂解和聚（adp -核糖）聚合酶（PARP）的蛋白水解降解，发现两种抗癌药物依托oposide和异黄酮A均可诱导结肠癌细胞株SW620凋亡。结果表明，两种药物均可上调SW620细胞的AChE。同时，JNK也被激活，c-Jun的表达和磷酸化在暴露于这两种药物的SW620细胞中增加。SAPK/JNK特异性抑制剂SP600125和靶向JNK1/2的小干扰RNA可阻断诱导的AChE mRNA和蛋白表达。转染腺病毒介导的显性阴性c-Jun也阻断了AChE表达的上调。综上所述，这些结果表明，在细胞凋亡过程中，通过c- jun依赖的机制，激活JNK通路可能介导了AChE的表达。
It has been shown that acetylcholinesterase (AChE) expression was induced during apoptosis and the anti-sense oligonucleotides and siRNA of AChE may prevent apoptosis in various cell types. However, the mechanisms underlying AChE upregulation remain elusive. We demonstrated here that c-Jun NH2-terminal kinase (JNK) could mediate AChE expression. In this study, both etoposide and excisanin A, two anticancer agents, induced apoptosis in colon cancer cell line SW620 as determined by Annexin V staining, the cleavage of caspase-3 and the proteolytic degradation of poly (ADP-ribose) polymerase (PARP). The results showed that both the agents upregulated AChE in SW620 cells. In the meantime, JNK was also activated and the expression and phosphorylation of c-Jun increased in SW620 cells exposed to the two agents. The induced AChE mRNA and protein expression could be blocked by SP600125, a specific inhibitor of SAPK/JNK, and small interfering RNA directed against JNK1/2. Transfection with adenovirus-mediated dominant negative c-Jun also blocked the upregulation of AChE expression. Together, these results suggest that AChE expression may be mediated by the activation of JNK pathway during apoptosis through a c-Jun-dependent mechanism.