title: The effect of Fenton reaction on protease-resistant prion protein (PrPSc) degradation and scrapie infectivity.
abstract: In prion diseases, metal imbalances in brain and/or metal substitutions for copper in prion protein suggest that metal-catalyzed oxidation (MCO) and oxidative stress may affect cellular function and accumulation of protease-resistant prion protein (PrP(Sc)). We examined the effect of metal-induced oxidative stress by Fenton reaction on prion protein with regard to its degradation, insolubility, and infectivity. Precipitation and insolubility of prion protein were induced by Fenton reaction in scrapie-infected brain homogenate. Results showed an increase in hydroxylation products (thiobarbituric acid reactive substances; TBARS) and a decrease of ferrous ion (Fe(2+)) levels after Fenton reaction. Efficiency of metal-induced oxidation was higher for Fe(2+) than Mn(2+). Compared to untreated samples, there was increased susceptibility to proteolytic degradation of PrP(Sc) after treatment with 3.12-12.5 mM Fe(2+)-Mn(2+)/H(2)O(2). Interestingly, we observed that Fenton reaction could extend incubation periods, indicating a decrease in scrapie infectivity. These results suggest that PrP(Sc) hydroxylation and degradation may affect PrP conversion and the pathogenesis of prion diseases.
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, Kyounggi-do, South Korea.
authors.forename: Seok-Joo
authors.initials: SJ
authors.lastname: Park
authors.forename: Nam-Ho
authors.initials: NH
authors.lastname: Kim
authors.forename: Byung-Hoon
authors.initials: BH
authors.lastname: Jeong
authors.forename: Jae-Kwang
authors.initials: JK
authors.lastname: Jin
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Choi
authors.forename: Young-Jae
authors.initials: YJ
authors.lastname: Park
authors.forename: Jae-Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Richard I
authors.initials: RI
authors.lastname: Carp
authors.forename: Yong-Sun
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D006861:Hydrogen Peroxide; D007150:Immunohistochemistry; D007501:Iron; D008297:Male; D008647:Mesocricetus; D018384:Oxidative Stress / Q000502:physiology*; D018620:PrPSc Proteins / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism* / Q000635:transmission*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: C045076:Fenton's reagent; D018620:PrPSc Proteins; D017392:Thiobarbituric Acid Reactive Substances; D006861:Hydrogen Peroxide; D007501:Iron