ER stress-mediated apoptosis induced by celastrol in cancer cells and important role of glycogen synthase kinase-3 beta in the signal network

doi:10.1038/cddis.2013.222

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 上海中药现代化研究中心

	ER stress-mediated apoptosis induced by celastrol in cancer cells and important role of glycogen synthase kinase-3 beta in the signal network
	Feng, L.2; Zhang, D.2; Fan, C.2; Ma, C.3; Yang, W.1; Meng, Y.2; Wu, W.2; Guan, S.2; Jiang, B.2; Yang, M.2
刊名	CELL DEATH & DISEASE
	2013-07
卷号	4
关键词	celastrol apoptosis endothelium reticulum proteomics bioinformatics
ISSN号	2041-4889
DOI	10.1038/cddis.2013.222
文献子类	Article
英文摘要	HeLa cells treated with celastrol, a natural compound with inhibitive effect on proteasome, exhibited increase in apoptotic rate and characteristics of apoptosis. To clarify the signal network activated by celastrol to induce apoptosis, both the direct target proteins and undirect target proteins of celastrol were searched in the present study. Proteasome catalytic subunit beta 1 was predicted by computational analysis to be a possible direct target of celastrol and confirmed by checking direct effect of celastrol on the activity of recombinant human proteasome subunit beta 1 in vitro. Undirect target-related proteins of celastrol were searched using proteomic studies including two-dimensional electrophoresis (2-DE) analysis and iTRAQ-based LC-MS analysis. Possible target-related proteins of celastrol such as endoplasmic reticulum protein 29 (ERP29) and mitochondrial import receptor Tom22 (TOM22) were found by 2-DE analysis of total cellular protein expression profiles. Further study showed that celastrol induced ER stress and ER stress inhibitor could ameliorate cell death induced by celastrol. Celastrol induced translocation of Bax into the mitochondria, which might be related to the upregulation of BH-3-only proteins such as BIM and the increase in the expression level of TOM22. To further search possible target-related proteins of celastrol in ER and ER-related fractions, iTRAQ-based LC-MS method was use to analyze protein expression profiles of ER/microsomal vesicles-riched fraction of cells with or without celastrol treatment. Based on possible target-related proteins found in both 2-DE analysis and iTRAQ-based LC-MS analysis, protein-protein interaction (PPI) network was established using bioinformatic analysis. The important role of glycogen synthase kinase-3 beta (GSK3 beta) in the signal cascades of celastrol was suggested. Pretreatment of LiCL, an inhibitor of GSK3 beta, could significantly ameliorate apoptosis induced by celastrol. On the basis of the results of the present study, possible signal network of celastrol activated by celastrol leading to apoptosis was predicted.
资助项目	Chinese Academy of Sciences[KSCX2-YW-R-166] ; Twelfth Five-Year National Science and Technology Support Program[2012BAI29B06] ; National Natural Science Foundation of China[30960450] ; Yunnan Provincial Science and Technology Department[2011FA022]
WOS关键词	INDUCED CASPASE-3 ACTIVATION ; THUNDER GOD VINE ; KINASE 3-BETA ; TOM COMPLEX ; MOLECULAR TARGETS ; HSP90 INHIBITOR ; OUTER-MEMBRANE ; IN-VIVO ; MITOCHONDRIA ; BAX
WOS研究方向	Cell Biology
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000322512100016
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277552]
专题	上海中药现代化研究中心天然药物化学研究室分析化学研究室药物安全性评价中心
通讯作者	Liu, X.
作者单位	1.Kunming Med Coll, Yunnan Pharmacol Labs Nat Prod, Kunming 650031, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China;
推荐引用方式 GB/T 7714	Feng, L.,Zhang, D.,Fan, C.,et al. ER stress-mediated apoptosis induced by celastrol in cancer cells and important role of glycogen synthase kinase-3 beta in the signal network[J]. CELL DEATH & DISEASE,2013,4.
APA	Feng, L..,Zhang, D..,Fan, C..,Ma, C..,Yang, W..,...&Guo, D..(2013).ER stress-mediated apoptosis induced by celastrol in cancer cells and important role of glycogen synthase kinase-3 beta in the signal network.CELL DEATH & DISEASE,4.
MLA	Feng, L.,et al."ER stress-mediated apoptosis induced by celastrol in cancer cells and important role of glycogen synthase kinase-3 beta in the signal network".CELL DEATH & DISEASE 4(2013).