科研之友
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摘要
Neuroblastoma-derived N2a-PK1 cells, fibroblastic LD9 cells, and CNS-derived CAD5 cells can be infected efficiently and pertly by various prion strains, as measured by the standard scrapie cell assay. Swainsonine, an inhibitor of Golgi alpha-mannosidase II that causes abnormal N-glycosylation, strongly inhibits infection of PK1 cells by RML, 79A and 22F, less so by 139A, and not at all by 221, prions, and it does not diminish propagation of any of these strains in LD9 or CADS cells. Misglycosylated PrPC formed in the presence of swainsonine is a good substrate for conversion to PrPSc, and misglycosylated PrPSc is fully able to trigger infection and seed the protein misfolding cyclic amplification reaction. Distinct subdones of PK1 cells mediate swainsonine inhibition to very different degrees, implicating misglycosylation of one or more host proteins in the inhibitory process. The use of swainsonine and other glycosylation inhibitors described herein enhances the ability of the cell panel assay to differentiate between prion strains. Moreover, as shown elsewhere, the susceptibility of prions to inhibition by swainsonine in PK1 cells is a mutable trait.
- 出版日期2011-11-25
