Document Detail


Conversion of trichosanthin-induced CD95 (Fas) type I into type II apoptotic signaling during Herpes simplex virus infection.
MedLine Citation:
PMID:  21723610     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 24.64μg/mL. When the same experiment was performed in HSV-1 infected HEp-2 cells, the EC(50) decreased to 3.01μg/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.
Authors:
Dongxu He; Kwowhei Yau; Xianhui He; Huanjing Shi; Yongtang Zheng; Siucheung Tam
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-30
Journal Detail:
Title:  Molecular immunology     Volume:  -     ISSN:  1872-9142     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-7-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905289     Medline TA:  Mol Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Affiliation:
School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
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