title: Prion protein conversion induced by trivalent iron in vesicular trafficking.
abstract: Iron dyshomeostasis has been observed in prion diseases; however, little is known regarding the contribution of the oxidation state of iron to prion protein (PrP) conversion. In this study, PrP(C)-deficient HpL3-4 cells were exposed to divalent [Fe(II)] or trivalent [Fe(III)] iron, followed by exogenous recombinant PrP (rPrP) treatment. We then analyzed the accumulation of internalized rPrP and its biochemical properties, including its resistance to both proteinase K (PK) digestion and detergent solubility. Fe(III), but not Fe(II), induced the accumulation of internalized rPrP, which was partially converted to detergent-insoluble and PK-resistant PrP (PrP(res)). The Fe(III)-induced PrP(res) generation required an intact cell structure, and it was hindered by U18666A, an inhibitor of vesicular trafficking, but not by NH4Cl, an inhibitor of endolysosomal acidification. These observations implicated that the Fe(III)-mediated PrP(res) conversion likely occurs during endosomal vesicular trafficking rather than in the acidic environment of lysosomes.
authors: Laboratory of Immunology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.
authors: Bo-Ran
authors: BR
authors: Choi
authors: Jeongmin
authors: J
authors: Lee
authors: Su Yeon
authors: SY
authors: Kim
authors: Inbeen
authors: I
authors: Yim
authors: Eun-Hee
authors: EH
authors: Kim
authors: Hee-Jong
authors: HJ
authors: Woo
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism*; D005290:Ferric Compounds / Q000378:metabolism* / Q000494:pharmacology; D006706:Homeostasis; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D017096:Prion Diseases / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: D005290:Ferric Compounds; D018621:PrPC Proteins; D011994:Recombinant Proteins; D007501:Iron