title: Molecular alterations in proteasomes of rat liver during aging result in altered proteolytic activities.
abstract: Aging induces alterations of tissue protein homoeostasis. To investigate one of the major systems catalysing intracellular protein degradation we have purified 20S proteasomes from rat liver of young (2 months) and aged (23 months) animals and separated them into three subpopulations containing different types of intermediate proteasomes with standard- and immuno-subunits. The smallest subpopulation ΙΙΙ and the major subpopulation Ι comprised proteasomes containing immuno-subunits β1i and β5i beside small amounts of standard-subunits, whereas proteasomes of subpopulation ΙΙ contained only β5i beside standard-subunits. In favour of a relative increase of the major subpopulation Ι, subpopulation ΙΙ and ΙΙΙ were reduced for about 55 % and 80 %, respectively, in aged rats. Furthermore, in all three 20S proteasome subpopulations from aged animals standard-active site subunits were replaced by immuno-subunits. Overall, this transformation resulted in a relative increase of immuno-subunit-containing proteasomes, paralleled by reduced activity towards short fluorogenic peptide substrates. However, depending on the substrate their hydrolysing activity of long polypeptide substrates was significantly higher or unchanged. Furthermore, our data revealed an altered MHC class I antigen-processing efficiency of 20S proteasomes from liver of aged rats. We therefore suggest that the age-related intramolecular alteration of hepatic proteasomes modifies its cleavage preferences without a general decrease of its activity. Such modifications could have implications on protein homeostasis as well as on MHC class I antigen presentation as part of the immunosenescence process.
authors.affiliation: Institute of Biochemistry, Charité-Universitätsmedizin Berlin, CCM, CharitéCrossOver, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Gohlke
authors.forename: Michele
authors.initials: M
authors.lastname: Mishto
authors.forename: Kathrin
authors.initials: K
authors.lastname: Textoris-Taube
authors.forename: Christin
authors.initials: C
authors.lastname: Keller
authors.forename: Carolin
authors.initials: C
authors.lastname: Giannini
authors.forename: Francesco
authors.initials: F
authors.lastname: Vasuri
authors.forename: Elisa
authors.initials: E
authors.lastname: Capizzi
authors.forename: Antonia
authors.initials: A
authors.lastname: D'Errico-Grigioni
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; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism*; D008297:Male; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D046988:Proteasome Endopeptidase Complex