Species-specific anti-apoptotic activity of cellular prion protein in a mouse PrP-deficient neuronal cell line transfected with mouse, hamster, and bovine Prnp.
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.
Wu
Guoying
G
Department of Molecular Immunology, School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
Nakajima
Kenta
K
Takeyama
Natsumi
N
Yukawa
Masayoshi
M
Taniuchi
Yojiro
Y
Sakudo
Akikazu
A
Onodera
Takashi
T
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
D016895:Culture Media, Serum-Free; D011328:Prions