title: Cytochalasin D enhances the accumulation of a protease-resistant form of prion protein in ScN2a cells: involvement of PI3 kinase/Akt signalling pathway.
abstract: The conversion of a host-encoded PrPsen (protease-sensitive cellular prion protein) into a PrPres (protease-resistant pathogenic form) is a key process in the pathogenesis of prion diseases, but the intracellular mechanisms underlying PrPres amplification in prion-infected cells remain elusive. To assess the role of cytoskeletal proteins in the regulation of PrPres amplification, the effects of cytoskeletal disruptors on PrPres accumulation in ScN2a cells that were persistently infected with the scrapie Chandler strain have been examined. Actin microfilament disruption with cytochalasin D enhanced PrPres accumulation in ScN2a cells. In contrast, the microtubule-disrupting agents, colchicine, nocodazole and paclitaxel, had no effect on PrPres accumulation. In addition, a PI3K (phosphoinositide 3-kinase) inhibitor, wortmannin and an Akt kinase inhibitor prevented the cytochalasin D-induced enhancement of PrPres accumulation. Cytochalasin D-induced extension of neurite-like processes might correlate with enhanced accumulation of PrPres. The results suggest that the actin cytoskeleton and PI3K/Akt pathway are involved in the regulation of PrPres accumulation in prion-infected cells.
authors.affiliation: National Institute of Agrobiological Sciences, Ibaraki, Japan.
authors.forename: Takato
authors.initials: T
authors.lastname: Takenouchi
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Iwamaru
authors.forename: Morikazu
authors.initials: M
authors.lastname: Imamura
authors.forename: Shigetomo
authors.initials: S
authors.lastname: Fukuhara
authors.forename: Shuei
authors.initials: S
authors.lastname: Sugama
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sato
authors.forename: Naoki
authors.initials: N
authors.lastname: Mochizuki
authors.forename: Makoto
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Shirou
authors.initials: S
authors.lastname: Mohri
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitani
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D015638:Cytochalasin D / Q000494:pharmacology*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D018620:PrPSc Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D015638:Cytochalasin D; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D018620:PrPSc Proteins; D051057:Proto-Oncogene Proteins c-akt