c-Jun NH2-terminal kinase activation is essential for up-regulation of LC3 during ceramide-induced autophagy in human nasopharyngeal carcinoma cells.
c-Jun NH2-terminal kinase activation is essential for up-regulation of LC3 during ceramide-induced autophagy in human nasopharyngeal carcinoma cells.
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DOI：
10.1186/1479-5876-9-161
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发表时间：
2011-09-26
影响因子：
7.4
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Sun T;Li D;Wang L;Xia L;Ma J;Guan Z;Feng G;Zhu X
自噬是一个动态的分解代谢过程，其特征是形成称为自噬体的双膜空泡。LC 3是酵母Atg 8的同源物，参与自噬体的形成，但其确切的调控机制仍有待阐明。通过Western blotting和共聚焦显微镜检测神经酰胺诱导的人鼻咽癌细胞系CNE 2和SUNE 1中LC 3的表达来确定自噬。Western blotting检测JNK和c-Jun的磷酸化形式，JNK活性特异性抑制剂SP 600125和针对JNK的siRNA阻断JNK/c-Jun通路。应用ChIP和荧光素酶报告基因分析来确定c-Jun是否参与LC 3转录的调控。神经酰胺处理的细胞表现出自噬和JNK通路激活的特征。抑制JNK通路可阻断神经酰胺诱导的自噬和LC 3表达上调。转录因子c-Jun参与了神经酰胺处理后LC 3的转录调控。神经酰胺可诱导人鼻咽癌细胞自噬，JNK通路的激活参与了神经酰胺诱导的自噬和LC 3表达。
Autophagy is a dynamic catabolic process characterized by the formation of double membrane vacuoles termed autophagosomes. LC3, a homologue of yeast Atg8, takes part in autophagosome formation, but the exact regulation mechanism of LC3 still needs to be elucidated. Ceramide-induced autophagy was determined by detecting LC3 expression with Western blotting and confocal microscopy in human nasopharyngeal carcinoma cell lines CNE2 and SUNE1. The activation of JNK pathway was assessed by Western blotting for phospho-specific forms of JNK and c-Jun. The JNK activity specific inhibitor, SP600125, and siRNA directed against JNK were used to block JNK/c-Jun pathway. ChIP and luciferase reporter analysis were applied to determine whether c-Jun was involved in the regulation of LC3 transcription. Ceramide-treated cells exhibited the characteristics of autophagy and JNK pathway activation. Inhibition of JNK pathway could block the ceramide-induced autophagy and the up-regulation of LC3 expression. Transcription factor c-Jun was involved in LC3 transcription regulation in response to ceramide treatment. Ceramide could induce autophagy in human nasopharyngeal carcinoma cells, and activation of JNK pathway was involved in ceramide-induced autophagy and LC3 expression.