Skip Navigation

Acta Biochimica et Biophysica Sinica 2009 41(1):42-53; doi:10.1093/abbs/gmn005
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Li, P.
Right arrow Articles by Dong, X.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, P.
Right arrow Articles by Dong, X.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences

Doppel-induced cytotoxicity in human neuronal SH-SY5Y cells is antagonized by the prion protein

Ping Li1, Chenfang Dong1, Yanjun Lei1,2, Bing Shan1, Xinli Xiao1,2, Huiying Jiang1, Xin Wang1, Chen Gao1, Qi Shi1, Kun Xu1,2, Chan Tian1, Jun Han1,* and Xiaoping Dong1,*

1 State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China
2 School of Medicine, Xi'an Jiao-Tong University, Xi'an 710061, China

* Corresponding authors: Xiaoping Dong: Tel/Fax, 86-10-83534616; E-mail, dongxp238{at}sina.com. Jun Han: Tel/Fax, 86-10-83559693; E-mail, hanjun_sci{at}yahoo.com.cn


  Abstract

Doppel (Dpl) is a prion (PrP)-like protein due to the structural and biochemical similarities; however, the natural functions of Dpl and PrP remain unclear. In this study, a 531-bp human PRND gene sequence encoding Dpl protein was amplified from human peripheral blood leucocytes. Full-length and various truncated human Dpl and PrP proteins were expressed and purified from Escherichia coli. Supplement of the full-length Dpl onto human neuroblastoma cell SH-SY5Y induced remarkable cytotoxicity, and the region responsible for its cytotoxicity was mapped at the middle segment of Dpl [amino acids (aa) 81–122]. Interestingly, Dpl-induced cytotoxicity was antagonized by the presence of full-length wild-type PrP. Analysis on fragments of PrP mutants showed that the N-terminal fragment (aa 23–90) of PrP was responsible for the protective activity. A truncated PrP (PrP{Delta}32–121) with similar secondary structure as Dpl induced Dpl-like cytotoxicity on SH-SY5Y cells. Furthermore, binding of copper ion could enhance the antagonizing effect of PrP on Dpl-induced cytotoxicity. Apoptosis assays revealed that cytotoxicity induced by Dpl occurred through an apoptotic mechanism. These results suggested that the function of Dpl is antagonistic to PrP rather than synergistic.

Keywords    Doppel; prion; cytotoxicity; apoptosis

Received: June 12, 2008; Accepted: August 6, 2008
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.