title: Age-related carbonylation of fibrocartilage structural proteins drives tissue degenerative modification.
abstract: Aging-related oxidative stress has been linked to degenerative modifications in different organs and tissues. Using redox proteomic analysis and illustrative tandem mass spectrometry mapping, we demonstrate oxidative posttranslational modifications in structural proteins of intervertebral discs (IVDs) isolated from aging mice. Increased protein carbonylation was associated with protein fragmentation and aggregation. Complementing these findings, a significant loss of elasticity and increased stiffness was measured in fibrocartilage from aging mice. Studies using circular dichroism and intrinsic tryptophan fluorescence revealed a significant loss of secondary and tertiary structures of purified collagens following oxidation. Collagen unfolding and oxidation promoted both nonenzymatic and enzymatic degradation. Importantly, induction of oxidative modification in healthy fibrocartilage recapitulated the biochemical and biophysical modifications observed in the aging IVD. Together, these results suggest that protein carbonylation, glycation, and lipoxidation could be early events in promoting IVD degenerative changes.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Scharf
authors.forename: Cristina C
authors.initials: CC
authors.lastname: Clement
authors.forename: Supansa
authors.initials: S
authors.lastname: Yodmuang
authors.forename: Aleksandra M
authors.initials: AM
authors.lastname: Urbanska
authors.forename: Sylvia O
authors.initials: SO
authors.lastname: Suadicani
authors.forename: David
authors.initials: D
authors.lastname: Aphkhazava
authors.forename: Mia M
authors.initials: MM
authors.lastname: Thi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Perino
authors.forename: John A
authors.initials: JA
authors.lastname: Hardin
authors.forename: Neil
authors.initials: N
authors.lastname: Cobelli
authors.forename: Gordana
authors.initials: G
authors.lastname: Vunjak-Novakovic
authors.forename: Laura
authors.initials: L
authors.lastname: Santambrogio
mesh_terms: D000375:Aging / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001696:Biomechanical Phenomena; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D051445:Fibrocartilage / Q000378:metabolism*; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D055959:Intervertebral Disc Degeneration / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D050050:Protein Carbonylation; D017510:Protein Folding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D059748:Proteolysis
chemical_list: D003094:Collagen; D020782:Matrix Metalloproteinases
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