title: Neuroendocrine cultured cells counteract persistent prion infection by down-regulation of PrPc.
abstract: Cell models for prion diseases are mainly of neuronal origin. However, the pathological isoform PrP(Sc) of cellular prion protein (PrP(c)) and prion infectivity are found in a variety of extraneural tissues in prion diseases. Although many cell types are not able to propagate PrP(Sc), little is known about cellular mechanism counteracting prion infection. It is desirable to identify neuronal or non-neuronal cell models that restrict PrP(Sc) generation or propagate PrP(Sc) only transiently. Neuroendocrine cells are derived from tumours forming the interface between endocrine and nervous system. We investigated the susceptibility of such murine cell lines to prion infection, which were in principle able to transiently propagate PrP(Sc). Surprisingly and in contrast to neuronal cells prion infection was abrogated by rapid and PrP(Sc)-specific down-regulation of PrP(c) expression upon exposure to prion-infected material. Cell lines described here provide novel models for studying PrP(c) regulation and intrinsic cellular defence mechanisms upon prion exposure.
authors.affiliation: Institute of Virology, Technical University of Munich, Trogerstr. 30, D-81675 Munich, Germany.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Aguib
authors.forename: Sabine
authors.initials: S
authors.lastname: Gilch
authors.forename: Carmen
authors.initials: C
authors.lastname: Krammer
authors.forename: Alexa
authors.initials: A
authors.lastname: Ertmer
authors.forename: Martin H
authors.initials: MH
authors.lastname: Groschup
authors.forename: Hermann M
authors.initials: HM
authors.lastname: Schätzl
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D007340:Insulinoma / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009490:Neurosecretory Systems / Q000378:metabolism / Q000473:pathology*; D010673:Pheochromocytoma / Q000378:metabolism / Q000473:pathology; D018621:PrPC Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000502:physiology; D018620:PrPSc Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017096:Prion Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012608:Scrapie / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control
chemical_list: D018621:PrPC Proteins; D018620:PrPSc Proteins