Conversion of trichosanthin-induced CD95 (Fas) type I into type II apoptotic signaling during Herpes simplex virus infection

	Conversion of trichosanthin-induced CD95 (Fas) type I into type II apoptotic signaling during Herpes simplex virus infection
	He DX 1; Yau KH 1; He XH 2; Shi HJ 2; Zheng YT 3; Tam SC*1; MTAM@cuhk.edu.hk
	2011
发表期刊	MOLECULAR IMMUNOLOGY
卷号	48 期号:15-16 页码:2000-2008
合作性质	其它
摘要	Trichosanthin (TCS) is a type I ribosome-inactivating protein with wide spectrum of pharmacological activities. It inhibits human immunodeficiency virus type 1 (HIV-1) and Herpes simplex virus type 1 (HSV-1) replication but the mechanism is not clear. From a previous study, TCS was found to be more cytotoxic to HIV-1 infected cells than uninfected cells. Similar finding was confirmed with HSV-1 in the present study. TCS induced cell death in HEp-2 cells and the EC(50) was 24.64 mu g/mL. When the same experiment was performed in HSV-1 infected HEp-2 cells, the EC(50) decreased to 3.01 mu g/mL. TCS appeared to cause more death and apoptosis in viral infected cells. This study explored plausible mechanism with respect to the apoptosis signal pathways. In uninfected cells, TCS induced CD95 (Fas)-mediated and caspase-8-dependent type I apoptosis. When cells were infected with HSV-1, apoptosis induced by TCS clearly switched to a more potent type II pathway. This involved mitochondrial depolarization and caspase-9 activation. The major evidences arose from studying the individual signals of the two apoptosis pathways in infected and uninfected cells. In addition, over expression of Bcl-2, which mainly affected the type II pathway reduced TCS induced apoptosis mostly in infected cells. This further demonstrated that the type II pathway was operating in infected cells. The reason for the switching is not entirely clear but it is well known that viral infection affects signal pathways especially those related to apoptosis. In conclusion, TCS selectively induces more apoptosis in HSV-1 infected cells than uninfected cells. The consequence of infection switches the TCS-induced apoptosis pathway from a CD95 (Fas) dependent type I to a more potent type II pathway mediated by mitochondrial depolarization and caspase-9 activation.
关键词	Cd95 (Fas) Apoptotic Signaling Type I/ii Apoptotic Pathway Trichosanthin Herpes Simplex Virus Type 1
资助者	We appreciate the funding support by the School of Biomedical Sciences of the Chinese University of Hong Kong. ; We appreciate the funding support by the School of Biomedical Sciences of the Chinese University of Hong Kong. ; We appreciate the funding support by the School of Biomedical Sciences of the Chinese University of Hong Kong. ; We appreciate the funding support by the School of Biomedical Sciences of the Chinese University of Hong Kong.
收录类别	SCI
语种	英语
资助者	We appreciate the funding support by the School of Biomedical Sciences of the Chinese University of Hong Kong. ; We appreciate the funding support by the School of Biomedical Sciences of the Chinese University of Hong Kong. ; We appreciate the funding support by the School of Biomedical Sciences of the Chinese University of Hong Kong. ; We appreciate the funding support by the School of Biomedical Sciences of the Chinese University of Hong Kong.
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/353002/6821
专题	科研部门_分子免疫药理学（郑永唐）
通讯作者	MTAM@cuhk.edu.hk
作者单位	1.School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China 2.Institute of Tissue Transplantation and Immunology, College of Life Science and Technology, Jinan University, Guangdong, China 3.Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, PR China
推荐引用方式 GB/T 7714	He DX,Yau KH,He XH,et al. Conversion of trichosanthin-induced CD95 (Fas) type I into type II apoptotic signaling during Herpes simplex virus infection[J]. MOLECULAR IMMUNOLOGY,2011,48(15-16):2000-2008.
APA	He DX.,Yau KH.,He XH.,Shi HJ.,Zheng YT.,...&MTAM@cuhk.edu.hk.(2011).Conversion of trichosanthin-induced CD95 (Fas) type I into type II apoptotic signaling during Herpes simplex virus infection.MOLECULAR IMMUNOLOGY,48(15-16),2000-2008.
MLA	He DX,et al."Conversion of trichosanthin-induced CD95 (Fas) type I into type II apoptotic signaling during Herpes simplex virus infection".MOLECULAR IMMUNOLOGY 48.15-16(2011):2000-2008.

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