NR ARAM
AU Luhr,K.M.; Nordström,E.K.; Low,P.; Kristensson,K.
TI Cathepsin B and L are involved in degradation of prions in GT1-1 neuronal cells
QU Neuroreport 2004 Jul 19; 15(10): 1663-7
PT journal article
AB In scrapie-infected cells, the abnormal isoform of the prion protein, PrPsc, accumulates in endosomes/lysosomes. In this study, the involvement of two lysosomal proteases, cathepsin B and L, in cellular processing of PrPsc was analyzed in immortalized neuronal gonadotropin-releasing hormone cells (GT1-1) infected with scrapie. Treatment with inhibitors of either cathepsin B or L resulted in accumulation of PrPsc. Such an increased accumulation also occurred when the activities of both cathepsins were inhibited using RNA interference. We conclude that cathepsin B and L are involved in the degradation of PrPsc in scrapie-infected GT1-1 cells and that they can compensate for each other's functions. This study shows that specific proteases, abundantly present in neurons, have the capacity to degrade PrPsc.
MH Animals; Blotting, Western/methods; Cathepsin B/antagonists & inhibitors/genetics/*metabolism; Cathepsins/antagonists & inhibitors/genetics/*metabolism; Cell Line; Comparative Study; Gonadorelin/metabolism; Hypothalamus; Mice; Neurons/*metabolism/virology; PrPsc Proteins/metabolism; Prions/*metabolism; RNA, Messenger/biosynthesis; RNA, Small Interfering/metabolism/pharmacology; Reverse Transcriptase Polymerase Chain Reaction/methods; Support, Non-U.S. Gov't; Transfection/methods
AD Department of Neuroscience B2:5, Retzius vag 8, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
SP englisch
PO England