NR AQHD
AU Choi,Y.G.; Kim,J.I.; Jeon,Y.C.; Park,S.J.; Choi,E.K.; Rubenstein,R.; Kascsak,R.J.; Carp,R.I.; Kim,Y.S.
TI Nonenzymatic glycation at the N terminus of pathogenic prion protein in transmissible spongiform encephalopathies
QU The Journal of Biological Chemistry 2004 Jul 16; 279(29): 30402-9
PT journal article
AB Transmissible spongiform encephalopathies (TSEs) are transmissible neurodegenerative diseases characterized by the accumulation of an abnormally folded prion protein, termed PrPsc, and the development of pathological features of astrogliosis, vacuolation, neuronal cell loss, and in some cases amyloid plaques. Although considerable structural characterization of prion protein has been reported, neither the method of conversion of cellular prion protein, PrPc, into the pathogenic isoform nor the post-translational modification processes involved is known. We report that in animal and human TSEs, one or more lysines at residues 23, 24, and 27 of PrPsc are covalently modified with advanced glycosylation end products (AGEs), which may be carboxymethyl-lysine (CML), one of the structural varieties of AGEs. The arginine residue at position 37 may also be modified with AGE, but not the arginine residue at position 25. This result suggests that nonenzymatic glycation is one of the post-translational modifications of PrPsc. Furthermore, immunostaining studies indicate that, at least in clinically affected hamsters, astrocytes are the first site of this glycation process.
IN Lesezeichen
MH Animals; Arginine/chemistry; Astrocytes; Binding, Competitive; Blotting, Western; Brain/metabolism; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Glycosylation; Hamsters; Human; Immunohistochemistry; Kinetics; Lysine/*analogs & derivatives/chemistry; Mice; Mice, Inbred C57BL; Models, Biological; Oxygen/metabolism; Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase/chemistry; Peptides/chemistry; PrPsc Proteins/chemistry; Precipitin Tests; Prion Diseases/*metabolism; Prions/*chemistry; Protein Isoforms; Protein Processing, Post-Translational; Protein Structure, Tertiary; Support, Non-U.S. Gov't
AD Ilsong Institute of Life Science, College of Medicine, Hallym University, Anyang, Kyeonggi-Do, Republic of Korea.
SP englisch
PO USA