TY - JOUR
T1 - Age-related carbonylation of fibrocartilage structural proteins drives tissue degenerative modification
AU - Scharf, Brian
AU - Clement, Cristina C.
AU - Yodmuang, Supansa
AU - Urbanska, Aleksandra M.
AU - Suadicani, Sylvia O.
AU - Aphkhazava, David
AU - Thi, Mia M.
AU - Perino, Giorgio
AU - Hardin, John A.
AU - Cobelli, Neil
AU - Vunjak-Novakovic, Gordana
AU - Santambrogio, Laura
N1 - Funding Information:
This work was supported by NIH grants (AB002520 and S10 RR020949) and the generous donations from Arnold Penner and the Jabez and Helen Hardin Foundation. We acknowledge MS Bioworks (Ann Arbor, MI) for the mass spectrometry service.
PY - 2013/7/25
Y1 - 2013/7/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84880862785&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880862785&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2013.06.006
DO - 10.1016/j.chembiol.2013.06.006
M3 - Article
C2 - 23890010
AN - SCOPUS:84880862785
SN - 1074-5521
VL - 20
SP - 922
EP - 934
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 7
ER -