Inhibition of the JNK/Bim pathway by Hsp70 prevents Bax activation in UV-induced apoptosis |
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Authors: | Li Hui Liu Lei Xing Da Chen Wei R |
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Institution: | MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China |
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Abstract: | Here we studied the mechanism by which heat shock protein 70 (Hsp70) prevents Bax activation during ultraviolet (UV)-induced apoptosis. UV treatment led to c-Jun N-terminal kinase (JNK) phosphorylation, Bim redistribution and subsequent Bax activation. Bim depletion caused a smaller reduction in apoptosis than that by JNK inhibition, indicating that Bim activation is not entirely responsible for induction of apoptosis and other mechanisms are involved. Hsp70 knockdown resulted in high levels of activated JNK and Bax, while Hsp70 overexpression inhibited these processes. These findings demonstrate that Hsp70 prevented Bax activation via inhibiting the JNK/Bim pathway. Simultaneously, increased binding of Hsp70 to Bax was observed. Collectively, our results for the first time demonstrate that Hsp70 prevents Bax activation both by inhibiting the JNK/Bim pathway and by interacting with Bax in UV-induced apoptosis. |
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Keywords: | LCSM laser confocal scanning microscopy JNK c-Jun N-terminal kinase CCK-8 Cell Counting Kit-8 CFP YFP DsRed and GFP cyan yellow red and green fluorescent protein FRET fluorescence resonance energy transfer Hsp70 heat shock protein 70 UV ultraviolet shRNA short hairpin RNA |
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