Cell density-dependent increase in the level of protease-resistant prion protein in prion-infected Neuro2a mouse neuroblastoma cells.
Cells persistently infected with prions continuously produce protease-resistant prion protein (PrP-res). Here, we show that the PrP-res level in prion-infected Neuro2a (N2a) neuroblastoma cells decreased to 50% of their initial level over the first 48 h and then recovered by 96 h after seeding. The level of cellular prion protein (PrP(C)) also appeared to fluctuate, but did not influence the fluctuation of the PrP-res level. Prion-infected N2a cells, co-cultured with a higher number of prion-unsusceptible cells, had twice as much PrP-res as those cultured without unsusceptible cells, suggesting that cell density influences the fluctuation of PrP-res as. Direct cell-to-cell contact between cells, rather than soluble factors, was involved in the cell density-dependent increase in the PrP-res level. The cholesterol content, which is known to influence PrP-res formation, also changed depending on cell density. Our data suggest that alterations in cellular microenvironments controlled by cell density influence PrP-res formation.
Nakamitsu
Satoshi
S
Laboratory of Prion Diseases, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.
Kurokawa
Aya
A
Yamasaki
Takeshi
T
Uryu
Masahide
M
Hasebe
Rie
R
Horiuchi
Motohiro
M
D000818:Animals; D002452:Cell Count; D045744:Cell Line, Tumor; D002477:Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009447:Neuroblastoma / Q000737:chemistry / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*
D011328:Prions; D010447:Peptide Hydrolases