Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-10-6
pubmed:abstractText
A hallmark in prion diseases is the conformational transition of the cellular prion protein (PrP(C)) into a pathogenic conformation, designated scrapie prion protein (PrP(Sc)), which is the essential constituent of infectious prions. Here, we show that epigallocatechin gallate (EGCG) and gallocatechin gallate, the main polyphenols in green tea, induce the transition of mature PrP(C) into a detergent-insoluble conformation distinct from PrP(Sc). The PrP conformer induced by EGCG was rapidly internalized from the plasma membrane and degraded in lysosomal compartments. Isothermal titration calorimetry studies revealed that EGCG directly interacts with PrP leading to the destabilizing of the native conformation and the formation of random coil structures. This activity was dependent on the gallate side chain and the three hydroxyl groups of the trihydroxyphenyl side chain. In scrapie-infected cells EGCG treatment was beneficial; formation of PrP(Sc) ceased. However, in uninfected cells EGCG interfered with the stress-protective activity of PrP(C). As a consequence, EGCG-treated cells showed enhanced vulnerability to stress conditions. Our study emphasizes the important role of PrP(C) to protect cells from stress and indicate efficient intracellular pathways to degrade non-native conformations of PrP(C).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1471-4159
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
107
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
218-29
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:18691383-Animals, pubmed-meshheading:18691383-Antioxidants, pubmed-meshheading:18691383-Catechin, pubmed-meshheading:18691383-Cell Death, pubmed-meshheading:18691383-Cell Line, Tumor, pubmed-meshheading:18691383-Drugs, Chinese Herbal, pubmed-meshheading:18691383-Endocytosis, pubmed-meshheading:18691383-Flavonoids, pubmed-meshheading:18691383-Humans, pubmed-meshheading:18691383-Lysosomes, pubmed-meshheading:18691383-Mice, pubmed-meshheading:18691383-Molecular Structure, pubmed-meshheading:18691383-Oxidative Stress, pubmed-meshheading:18691383-Phenols, pubmed-meshheading:18691383-Polyphenols, pubmed-meshheading:18691383-PrPC Proteins, pubmed-meshheading:18691383-PrPSc Proteins, pubmed-meshheading:18691383-Prion Diseases, pubmed-meshheading:18691383-Protein Conformation, pubmed-meshheading:18691383-Signal Transduction, pubmed-meshheading:18691383-Solubility
pubmed:year
2008
pubmed:articleTitle
Green tea extracts interfere with the stress-protective activity of PrP and the formation of PrP.
pubmed:affiliation
Department of Biochemistry, Neurobiochemistry, Ludwig-Maximilians-Universität München, München, Germany.
pubmed:publicationType
Journal Article