Age-related carbonylation of fibrocartilage structural proteins drives tissue degenerative modification

Brian Scharf, Cristina C. Clement, Supansa Yodmuang, Aleksandra M. Urbanska, Sylvia O. Suadicani, David Aphkhazava, Mia M. Thi, Giorgio Perino, John A. Hardin, Neil J. Cobelli, Gordana Vunjak-Novakovic, Laura Santambrogio

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)922-934
Number of pages13
JournalChemistry and Biology
Volume20
Issue number7
DOIs
StatePublished - Jul 25 2013

Fingerprint

Protein Carbonylation
Fibrocartilage
Carbonylation
Intervertebral Disc
Collagen
Aging of materials
Tissue
Intervertebral Disc Degeneration
Elasticity
Post Translational Protein Processing
Circular Dichroism
Tandem Mass Spectrometry
Tryptophan
Proteomics
Oxidation-Reduction
Proteins
Oxidative Stress
Fluorescence
Oxidation
Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Molecular Biology
  • Clinical Biochemistry
  • Molecular Medicine
  • Pharmacology

Cite this

Age-related carbonylation of fibrocartilage structural proteins drives tissue degenerative modification. / Scharf, Brian; Clement, Cristina C.; Yodmuang, Supansa; Urbanska, Aleksandra M.; Suadicani, Sylvia O.; Aphkhazava, David; Thi, Mia M.; Perino, Giorgio; Hardin, John A.; Cobelli, Neil J.; Vunjak-Novakovic, Gordana; Santambrogio, Laura.

In: Chemistry and Biology, Vol. 20, No. 7, 25.07.2013, p. 922-934.

Research output: Contribution to journalArticle

Scharf, B, Clement, CC, Yodmuang, S, Urbanska, AM, Suadicani, SO, Aphkhazava, D, Thi, MM, Perino, G, Hardin, JA, Cobelli, NJ, Vunjak-Novakovic, G & Santambrogio, L 2013, 'Age-related carbonylation of fibrocartilage structural proteins drives tissue degenerative modification', Chemistry and Biology, vol. 20, no. 7, pp. 922-934. https://doi.org/10.1016/j.chembiol.2013.06.006
Scharf, Brian ; Clement, Cristina C. ; Yodmuang, Supansa ; Urbanska, Aleksandra M. ; Suadicani, Sylvia O. ; Aphkhazava, David ; Thi, Mia M. ; Perino, Giorgio ; Hardin, John A. ; Cobelli, Neil J. ; Vunjak-Novakovic, Gordana ; Santambrogio, Laura. / Age-related carbonylation of fibrocartilage structural proteins drives tissue degenerative modification. In: Chemistry and Biology. 2013 ; Vol. 20, No. 7. pp. 922-934.
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