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Chemotherapy-induced pyroptosis is mediated by BAK/BAX-caspase-3-GSDME pathway and inhibited by 2-bromopalmitate

文献类型：期刊论文

作者Hu, Lei1,2,3; Chen, Meng1,2,3; Chen, Xueran1,3; Zhao, Chenggang1,2,3; Fang, Zhiyou1,3; Wang, Hongzhi1,3; Dai, Haiming1,3
刊名CELL DEATH & DISEASE
出版日期2020-04-24
卷号11
ISSN号2041-4889
DOI10.1038/s41419-020-2476-2
通讯作者Dai, Haiming(daih@cmpt.ac.cn)
英文摘要Many chemotherapy treatments induce apoptosis or pyroptosis through BAK/BAX-dependent mitochondrial pathway. BAK/BAX activation causes the mitochondrial outer membrane permeabilization (MOMP), which induces the activation of pro-apoptotic caspase cascade. GSDME cleavage by the pro-apoptotic caspases determines whether chemotherapy drug treatments induce apoptosis or pyroptosis, however, its regulation mechanisms are not clear. In this study, we showed that TNF alpha +CHX and navitoclax-induced cancer cell pyroptosis through a BAK/BAX-caspase-3-GSDME signaling pathway. GSDME knockdown inhibited the pyroptosis, suggesting the essential role of GSDME in this process. Interestingly, GSDME was found to be palmitoylated on its C-terminal (GSDME-C) during chemotherapy-induced pyroptosis, while 2-bromopalmitate (2-BP) could inhibit the GSDME-C palmitoylation and chemotherapy-induced pyroptosis. Mutation of palmitoylation sites on GSDME also diminished the pyroptosis induced by chemotherapy drugs. Moreover, 2-BP treatment increased the interaction between GSDME-C and GSDME-N, providing a potential mechanism of this function. Further studies indicated several ZDHHC proteins including ZDHHC-2,7,11,15 could interact with and palmitoylate GSDME. Our findings offered new targets to achieve the transformation between chemotherapy-induced pyroptosis and apoptosis.
WOS关键词CELL-DEATH ; GASDERMIN D ; INFLAMMATORY CASPASES ; MOLECULAR-MECHANISMS ; DFNA5 GENE ; PROTEIN ; PALMITOYLATION ; ACTIVATION ; GSDMD ; CLEAVAGE
资助项目National Natural Science Foundation of China[21772201] ; National Natural Science Foundation of China[81572948] ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology[2018CXFX007]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000530255700012
出版者NATURE PUBLISHING GROUP
资助机构National Natural Science Foundation of China ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/103413]  
专题中国科学院合肥物质科学研究院
通讯作者Dai, Haiming
作者单位1.Chinese Acad Sci, Ctr Med Phys & Technol, Anhui Prov Key Lab Med Phys & Technol, Hefei Inst Phys Sci, Hefei 230031, Peoples R China
2.Univ Sci & Technol China, Hefei 230026, Peoples R China
3.Chinese Acad Sci, Hefei Canc Hosp, Hefei 230031, Peoples R China
推荐引用方式
GB/T 7714		 Hu, Lei,Chen, Meng,Chen, Xueran,et al. Chemotherapy-induced pyroptosis is mediated by BAK/BAX-caspase-3-GSDME pathway and inhibited by 2-bromopalmitate[J]. CELL DEATH & DISEASE,2020,11.
APA Hu, Lei.,Chen, Meng.,Chen, Xueran.,Zhao, Chenggang.,Fang, Zhiyou.,...&Dai, Haiming.(2020).Chemotherapy-induced pyroptosis is mediated by BAK/BAX-caspase-3-GSDME pathway and inhibited by 2-bromopalmitate.CELL DEATH & DISEASE,11.
MLA Hu, Lei,et al."Chemotherapy-induced pyroptosis is mediated by BAK/BAX-caspase-3-GSDME pathway and inhibited by 2-bromopalmitate".CELL DEATH & DISEASE 11(2020).

入库方式： OAI收割

来源：合肥物质科学研究院

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