title: Overexpressed protein disulfide isomerase in brains of patients with sporadic Creutzfeldt-Jakob disease.
abstract: Earlier studies have failed to detect covalent modifications in beta-sheet-rich scrapie isoform prion protein (PrP(Sc)) and have concluded that the conversion of alpha-helix-rich cellular form prion protein (PrP(C)) to PrP(Sc) represents purely conformational transition not involving chemical reactions. However, recent studies have shown that the intradisulfide bond of PrP(C) can play an important role for instability and conformational change to PrP(Sc). Interestingly, we found overexpressed protein disufide isomerase (PDI) in brains of sporadic Creutzfeldt-Jakob disease (sCJD, human prion disease) patients using two dimensional electrophoresis and Western blot analysis but not in other neurodegenerative disorders as Down Syndrome and Alzheimer's disease. However, proteinase K digestion and plasminogen binding assay of brain homogenates incubated with PDI suggest that PDI has no effect on either proteinase resistance or conformational change of PrP. Overexpression of PDI protein in sCJD brain may simply reflect a cellular defense response against the altered prion protein.
authors.affiliation: Department of Pediatrics, University of Vienna, Waehringer Guertel 18, A-1090 Vienna, Austria.
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
authors.forename: Kurt
authors.initials: K
authors.lastname: Krapfenbauer
authors.forename: Nigel
authors.initials: N
authors.lastname: Cairns
authors.forename: Girma
authors.initials: G
authors.lastname: Belay
authors.forename: Michal
authors.initials: M
authors.lastname: Bajo
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D002531:Cerebellum / Q000201:enzymology / Q000378:metabolism; D007562:Creutzfeldt-Jakob Syndrome / Q000201:enzymology* / Q000378:metabolism; D004314:Down Syndrome / Q000201:enzymology / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000737:chemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010449:Peptide Mapping / Q000379:methods; D010751:Phosphopyruvate Hydratase / Q000737:chemistry; D018621:PrPC Proteins / Q000032:analysis; D018620:PrPSc Proteins / Q000032:analysis* / Q000737:chemistry; D011487:Protein Conformation; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D018709:Statistics, Nonparametric
chemical_list: D005904:Glial Fibrillary Acidic Protein; D018621:PrPC Proteins; D018620:PrPSc Proteins; D010751:Phosphopyruvate Hydratase; D019704:Protein Disulfide-Isomerases