PMID- 11100979
OWN - NLM
STAT- MEDLINE
DCOM- 20010531
LR  - 20191025
IS  - 0272-4340 (Print)
IS  - 0272-4340 (Linking)
VI  - 20
IP  - 6
DP  - 2000 Dec
TI  - Early appearance but lagged accumulation of detergent-insoluble prion protein in 
      the brains of mice inoculated with a mouse-adapted Creutzfeldt-Jakob disease 
      agent.
PG  - 717-30
AB  - 1. To elucidate mechanisms for the generation of the detergent-insoluble, 
      proteinase K-resistant prion protein (PrP(Sc)) from the detergent-soluble, 
      proteinase K-sensitive PrP (PrP(C)) and the replication of the infectious agent 
      in prion diseases, we followed the kinetics of detergent-insoluble PrP and 
      PrP(Sc) levels, infectious titers, and associated pathological changes in the 
      brains of mice inoculated with a mouse-adapted Creutzfeldt Jakob disease agent. 
      2. PrP(Sc) in brain homogenate and detergent-insoluble PrP enriched by two-cycle 
      ultracentrifugation were detected by immunoblotting and their relative amounts 
      were estimated according to a standard curve plotted between the amount of PrP 
      and signal intensity on immunoblotting. The titer of infectivity was determined 
      by the incubation periods of mice inoculated with the unfractionated homogenate 
      on the basis of a standard curve plotted between the titer and incubation period. 
      3. Detergent-insoluble PrP became detectable 4 weeks postinoculation (p.i.) well 
      before the detection of PrP(Sc). The low level of detergent-insoluble PrP 
      continued until dramatic accumulation occurred at 14 weeks p.i., correlating well 
      with the accumulation of PrP(Sc) and development of pathological changes. The 
      infectious titer was undetectable at 4 weeks p.i. and its logarithmic increase 
      occurred 10 weeks p.i. preceding the logarithmic accumulation of PrPs. 4. The lag 
      time of detergent-insoluble PrP accumulation and the discrepancy between 
      infectious titers and PrPs observed during the early period after inoculation 
      suggest a slow and rate-limiting step for the detergent-insoluble PrP to become 
      the infectious agent-associated PrP(Sc).
FAU - Nakaoke, R
AU  - Nakaoke R
AD  - Department of Bacteriology, Nagasaki University School of Medicine, Japan.
FAU - Sakaguchi, S
AU  - Sakaguchi S
FAU - Atarashi, R
AU  - Atarashi R
FAU - Nishida, N
AU  - Nishida N
FAU - Arima, K
AU  - Arima K
FAU - Shigematsu, K
AU  - Shigematsu K
FAU - Katamine, S
AU  - Katamine S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Mol Neurobiol
JT  - Cellular and molecular neurobiology
JID - 8200709
RN  - 0 (PrPSc Proteins)
RN  - 0 (Prions)
RN  - EC 3.4.21.64 (Endopeptidase K)
SB  - IM
MH  - Animals
MH  - Brain/*metabolism/*pathology
MH  - Creutzfeldt-Jakob Syndrome/*metabolism/pathology
MH  - Disease Models, Animal
MH  - Endopeptidase K
MH  - Immunoblotting
MH  - Kinetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred Strains
MH  - PrPSc Proteins/isolation & purification/*metabolism
MH  - Prions/isolation & purification/*metabolism
MH  - Ultracentrifugation
EDAT- 2000/12/02 11:00
MHDA- 2001/06/02 10:01
CRDT- 2000/12/02 11:00
PHST- 2000/12/02 11:00 [pubmed]
PHST- 2001/06/02 10:01 [medline]
PHST- 2000/12/02 11:00 [entrez]
AID - 10.1023/a:1007054909662 [doi]
PST - ppublish
SO  - Cell Mol Neurobiol. 2000 Dec;20(6):717-30. doi: 10.1023/a:1007054909662.