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Lactoferrin induces cell surface retention of prion protein and inhibits prion accumulation
Author(s) -
Iwamaru Yoshifumi,
Shimizu Yoshihisa,
Imamura Morikazu,
Murayama Yuichi,
Endo Ryo,
Tagawa Yuichi,
UshikiKaku Yuko,
Takenouchi Takato,
Kitani Hiroshi,
Mohri Shirou,
Yokoyama Takashi,
Okada Hiroyuki
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05628.x
Subject(s) - scrapie , lactoferrin , internalization , gene isoform , chemistry , cell culture , cell , pathogenesis , glycoprotein , in vitro , amyloid (mycology) , transferrin , proteinase k , biology , prion protein , microbiology and biotechnology , biochemistry , dna , disease , immunology , gene , medicine , inorganic chemistry , genetics , pathology
Prion diseases are fatal neurodegenerative disorders, and the conformational conversion of normal cellular prion protein (PrP C ) into its pathogenic, amyloidogenic isoform (PrP Sc ) is the essential event in the pathogenesis of these diseases. Lactoferrin (LF) is a cationic iron‐binding glycoprotein belonging to the transferrin (TF) family, which accumulates in the amyloid deposits in the brain in neurodegenerative disorders, such as Alzheimer’s disease and Pick’s disease. In the present study, we have examined the effects of LF on PrP Sc formation by using cell culture models. Bovine LF inhibited PrP Sc accumulation in scrapie‐infected cells in a time‐ and dose‐dependent manner, whereas TF was not inhibitory. Bioassays of LF‐treated cells demonstrated prolonged incubation periods compared with non‐treated cells indicating a reduction of prion infectivity. LF mediated the cell surface retention of PrP C by diminishing its internalization and was capable of interacting with PrP C in addition to PrP Sc . Furthermore, LF partially inhibited the formation of protease‐resistant PrP as determined by the protein misfolding cyclic amplification assay. Our results suggest that LF has multifunctional antiprion activities.