title: Phage-displayed antibodies for the detection of glycated proteasome in aging cells.
abstract: Accumulation of posttranslationally damaged proteins during aging could explain the decline of cell performance with age. N(epsilon)-carboxymethyllysine (CML) is the major glycation product on damaged proteins, causing dysfunction and cross-linking. The proteasome, a multicatalytic degradation complex, is one of the pathways for eliminating damaged proteins, and thus regulating their accumulation within the cell. However, the proteinase activities of the proteasome decline during aging. This may be due to posttranslational modifications of the subunits forming the proteasome complex. Using phage display technology, we have selected 16 single-chain variable fragments (scFv) recognizing the CML-modified alpha7 subunit of the proteasome. Using one of them, Ab3, we have observed a five-fold increase of CML-alpha7 in old human skin fibroblasts in comparison with young fibroblasts and telomerase-immortalized bone marrow cells (hTERT-BMCs).
authors.affiliation: Danish Centre of Molecular Gerontology, Department of Molecular Biology, University of Aarhus, Denmark.
authors.forename: Regina
authors.initials: R
authors.lastname: Gonzalez-Dosal
authors.forename: Morten Draeby
authors.initials: MD
authors.lastname: Sørensen
authors.forename: Brian F C
authors.initials: BF
authors.lastname: Clark
authors.forename: Suresh I S
authors.initials: SI
authors.lastname: Rattan
authors.forename: Peter
authors.initials: P
authors.lastname: Kristensen
mesh_terms: D000906:Antibodies / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology; D002461:Cell Line, Transformed; D016922:Cellular Senescence / Q000502:physiology*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D019151:Peptide Library; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D012867:Skin / Q000166:cytology; D019098:Telomerase / Q000378:metabolism
chemical_list: D000906:Antibodies; D019151:Peptide Library; D019098:Telomerase; D046988:Proteasome Endopeptidase Complex