The effect of Fenton reaction on protease-resistant prion protein (PrPSc) degradation and scrapie infectivity.
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.
Park
Seok-Joo
SJ
Ilsong Institute of Life Science, Hallym University, Anyang, Kyounggi-do, South Korea.
Kim
Nam-Ho
NH
Jeong
Byung-Hoon
BH
Jin
Jae-Kwang
JK
Choi
Jin-Kyu
JK
Park
Young-Jae
YJ
Kim
Jae-Il
JI
Carp
Richard I
RI
Kim
Yong-Sun
YS
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
C045076:Fenton's reagent; D018620:PrPSc Proteins; D017392:Thiobarbituric Acid Reactive Substances; D006861:Hydrogen Peroxide; D007501:Iron