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 Cobelli, Gordana Vunjak-Novakovic, Laura Santambrogio

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24 Scopus citations

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

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ASJC Scopus subject areas

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

Cite this

Scharf, B., Clement, C. C., Yodmuang, S., Urbanska, A. M., Suadicani, S. O., Aphkhazava, D., Thi, M. M., Perino, G., Hardin, J. A., Cobelli, N., Vunjak-Novakovic, G., & Santambrogio, L. (2013). Age-related carbonylation of fibrocartilage structural proteins drives tissue degenerative modification. Chemistry and Biology, 20(7), 922-934. https://doi.org/10.1016/j.chembiol.2013.06.006