Age-related carbonylation of fibrocartilage structural proteins drives tissue degenerative modification. Academic Article uri icon

Overview

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.

publication date

  • July 25, 2013

Research

keywords

  • Aging
  • Fibrocartilage
  • Intervertebral Disc
  • Intervertebral Disc Degeneration
  • Protein Carbonylation

Identity

PubMed Central ID

  • PMC3758909

Scopus Document Identifier

  • 84880862785

Digital Object Identifier (DOI)

  • 10.1016/j.chembiol.2013.06.006

PubMed ID

  • 23890010

Additional Document Info

volume

  • 20

issue

  • 7