title: Poly-Ub-substrate-degradative activity of 26S proteasome is not impaired in the aging rat brain.
abstract: Proteostasis is critical for the maintenance of life. In neuronal cells an imbalance between protein synthesis and degradation is thought to be involved in the pathogenesis of neurodegenerative diseases during aging. Partly, this seems to be due to a decrease in the activity of the ubiquitin-proteasome system, wherein the 20S/26S proteasome complexes catalyse the proteolytic step. We have characterised 20S and 26S proteasomes from cerebrum, cerebellum and hippocampus of 3 weeks old (young) and 24 month old (aged) rats. Our data reveal that the absolute amount of the proteasome is not dfferent between both age groups. Within the majority of standard proteasomes in brain the minute amounts of immuno-subunits are slightly increased in aged rat brain. While this goes along with a decrease in the activities of 20S and 26S proteasomes to hydrolyse synthetic fluorogenic tripeptide substrates from young to aged rats, the capacity of 26S proteasomes for degradation of poly-Ub-model substrates and its activation by poly-Ub-substrates is not impaired or even slightly increased in brain of aged rats. We conclude that these alterations in proteasome properties are important for maintaining proteostasis in the brain during an uncomplicated aging process.
authors.affiliation: Institut für Biochemie, Charité-Universitätsmedizin-Berlin, Berlin, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Giannini
authors.forename: Alexander
authors.initials: A
authors.lastname: Kloß
authors.forename: Sabrina
authors.initials: S
authors.lastname: Gohlke
authors.forename: Michele
authors.initials: M
authors.lastname: Mishto
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Nicholson
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sheppard
authors.forename: Peter-Michael
authors.initials: PM
authors.lastname: Kloetzel
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Dahlmann
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000201:enzymology; D054022:Cerebrum / Q000201:enzymology; D004591:Electrophoresis, Polyacrylamide Gel; D006624:Hippocampus / Q000201:enzymology; D006868:Hydrolysis; D008297:Male; D025821:Polyubiquitin / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D059748:Proteolysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity
chemical_list: D021122:Protein Subunits; D025821:Polyubiquitin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease