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Calnexin inhibits thermal aggregation and neurotoxicity of prion protein
Author(s) -
Wang Wenxi,
Chen Rui,
Luo Kan,
Wu Di,
Huang Liqin,
Huang Tao,
Xiao Gengfu
Publication year - 2010
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22698
Subject(s) - calnexin , chaperone (clinical) , endoplasmic reticulum , microbiology and biotechnology , scrapie , protein aggregation , in vitro , chemistry , gene isoform , flow cytometry , cytotoxicity , immunoprecipitation , biology , biochemistry , calreticulin , prion protein , medicine , disease , pathology , gene
Prion diseases are fatal neurodegenerative disorder associated with the conversion of the cellular isoform of the prion protein (PrP C ) into the infectious scrapie isoform (PrP Sc ). Deposition of misfolded prion proteins (PrP) on certain regions of brain can result in prion diseases. As a membrane‐bound chaperone of the endoplasmic reticulum (ER), calnexin ensures the proper folding and quality control of newly synthesized proteins. Using purified components in vitro, calnexin associated with many proteins and suppresses their thermal aggregation effectively. We for the first time analyzed PrP‐calnexin interaction. The immunoprecipitation, confocal microscope and native polyacrylamide‐gel electrophoresis results indicated that calnexin could bind PrP both in vitro and in vivo. The turbidity result showed that calnexin could supress thermal aggregation of PrP. MTT, flow cytometry (FCM) and caspase activity studies demonstrated that calnexin prevent caspase‐3‐mediated cytotoxicity induced by PrP. These results implied that calnexin is potentially beneficial for the resistance of prion diseases. J. Cell. Biochem. 111: 343–349, 2010. © 2010 Wiley‐Liss, Inc.