Ceramide Promotes Apoptosis in Lung Cancer-Derived A549 Cells by a Mechanism Involving c-Jun NH2-Terminal Kinase
Ceramide Promotes Apoptosis in Lung Cancer-Derived A549 Cells by a Mechanism Involving c-Jun NH2-Terminal Kinase
Speaker：鄭智仁 Time：PM 3:00-4:00；4/20/2005
Commentator：林秋烽 博士 Place：601
Abstract：
Ceramide is produced in response to stress stimuli, including chemotherapeutic drugs, growth factor withdrawal, or irradiation. Ceramide activates a variety of protein kinases and phopshatses that initiate the stress-induced signaling pathways. The authors have reported that ceramide promotes apoptosis of A549 cells by a mechanism involving c-Jun NH2-terminal kinases (JNKs). This study thus was designed to identify the responsible JNK-mediated pathways. The tested JNK target proteins included c-Jun, Bcl-XL, and Bim. The results of the experiments show that phosphorylation of c-Jun is inhibited by ceramide, suggesting that JNK-mediated phosphorylation of c-Jun is not likely involved in ceramide-induced apoptosis. On the contrary, ceramide promotes JNK phosphorylation of Bim, but not Bcl-XL, and induces translocalization of active JNK from nucleus to the cytoplasm and mitochondrial fractions. The translocalization of JNK was parallel with alterations of phosphorylation status of c-Jun and Bim. In addition, ceramide also induced translocalization of Bim to the mitochondria. Given that mitochondrial localization of Bim was related to apoptosis, the current study suggests that Bim may involve in JNK-mediated apoptosis in A549 cells induced by ceramide.
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