title: Species-specific anti-apoptotic activity of cellular prion protein in a mouse PrP-deficient neuronal cell line transfected with mouse, hamster, and bovine Prnp.
abstract: The neuroprotective function of prion protein (PrP) was revealed first by the fact that reintroduction of the mouse prion protein gene (Prnp) into a mouse Prnp(-/-) neuronal cell line, HpL3-4, could prevent apoptosis induced by serum deprivation. In the present study, the anti-apoptotic activities of mouse, hamster, and bovine PrP were compared by expressing mouse PrP (MoPrP), hamster PrP (HaPrP), and bovine PrP (BoPrP) in HpL3-4 cells, respectively. Morphological analysis and DNA fragmentation assays demonstrated that HpL3-4 cells expressing HaPrP, BoPrP, and empty vector (EM) showed the typical features of apoptosis with DNA laddering and apoptotic bodies after serum deprivation, whereas HpL3-4 cells expressing MoPrP showed decreased levels of apoptosis in comparison. The levels of histone-associated DNA fragments (mono- and oligonucleosomes) in the cytosol fractions of the cells correlated with the levels of DNA laddering. These results indicate a species-specific anti-apoptotic function of PrP exists, suggesting that the interaction of the mouse PrP with mouse host factors is required for its anti-apoptotic activity.
authors.affiliation: Department of Molecular Immunology, School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Guoying
authors.initials: G
authors.lastname: Wu
authors.forename: Kenta
authors.initials: K
authors.lastname: Nakajima
authors.forename: Natsumi
authors.initials: N
authors.lastname: Takeyama
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yukawa
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Taniuchi
authors.forename: Akikazu
authors.initials: A
authors.lastname: Sakudo
authors.forename: Takashi
authors.initials: T
authors.lastname: Onodera
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002417:Cattle; D002460:Cell Line; D006224:Cricetinae; D016895:Culture Media, Serum-Free; D053938:DNA Fragmentation / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011328:Prions / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013045:Species Specificity; D013223:Statistics as Topic; D014162:Transfection / Q000379:methods
chemical_list: D016895:Culture Media, Serum-Free; D011328:Prions