Oxidative damage to collagen and related substrates by metal ion/hydrogen peroxide systems: random attack or site-specific damage?
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Oxidative damage to collagen and related substrates by metal ion/hydrogen peroxide systems : random attack or site-specific damage? / Hawkins, C L; Davies, Michael Jonathan.
In: B B A - Reviews on Cancer, Vol. 1360, No. 1, 27.02.1997, p. 84-96.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Oxidative damage to collagen and related substrates by metal ion/hydrogen peroxide systems
T2 - random attack or site-specific damage?
AU - Hawkins, C L
AU - Davies, Michael Jonathan
PY - 1997/2/27
Y1 - 1997/2/27
N2 - Degradation of collagen by oxidant species may play an important role in the progression of rheumatoid arthritis. Whilst the overall effects of this process are reasonably well defined, little is known about the sites of attack, the nature of the intermediates, or the mechanism(s) of degradation. In this study electron paramagnetic resonance spectroscopy with spin trapping has been used to identify radicals formed on collagen and related materials by metal ion-H2O2 mixtures. Attack of the hydroxyl radical, from a Fe(II)-H2O2 redox couple, on collagen peptides gave signals from both side chain (.CHR'R"), and alpha-carbon[.C(R)(NH-)CO-,R = side-chain]radicals. Reaction with collagen gave both broad anisotropic signals, from high-molecular-weight protein-derived radicals, and isotropic signals from mobile species. The latter may be low-molecular-weight fragments, or mobile side-chain species; these signals are similar to those from the alpha-carbon site of peptides and the side-chain of lysine. Enzymatic digestion of the large, protein-derived, species releases similar low-molecular-weight adducts. The metal ion employed has a dramatic effect on the species observed. With Cu(I)-H2O2 or Cu(II)-H2O2 instead of Fe(II)-H2O2, evidence has been obtained for: i) altered sites of attack and fragmentation, ii) C-terminal decarboxylation, and iii) hydrogen abstraction at N-terminal alpha-carbon sites. This altered behaviour is believed to be due to the binding of copper ions to some substrates and hence site-specific damage. This has been confirmed in some cases by electron paramagnetic resonance studies of the Cu(II) ions.
AB - Degradation of collagen by oxidant species may play an important role in the progression of rheumatoid arthritis. Whilst the overall effects of this process are reasonably well defined, little is known about the sites of attack, the nature of the intermediates, or the mechanism(s) of degradation. In this study electron paramagnetic resonance spectroscopy with spin trapping has been used to identify radicals formed on collagen and related materials by metal ion-H2O2 mixtures. Attack of the hydroxyl radical, from a Fe(II)-H2O2 redox couple, on collagen peptides gave signals from both side chain (.CHR'R"), and alpha-carbon[.C(R)(NH-)CO-,R = side-chain]radicals. Reaction with collagen gave both broad anisotropic signals, from high-molecular-weight protein-derived radicals, and isotropic signals from mobile species. The latter may be low-molecular-weight fragments, or mobile side-chain species; these signals are similar to those from the alpha-carbon site of peptides and the side-chain of lysine. Enzymatic digestion of the large, protein-derived, species releases similar low-molecular-weight adducts. The metal ion employed has a dramatic effect on the species observed. With Cu(I)-H2O2 or Cu(II)-H2O2 instead of Fe(II)-H2O2, evidence has been obtained for: i) altered sites of attack and fragmentation, ii) C-terminal decarboxylation, and iii) hydrogen abstraction at N-terminal alpha-carbon sites. This altered behaviour is believed to be due to the binding of copper ions to some substrates and hence site-specific damage. This has been confirmed in some cases by electron paramagnetic resonance studies of the Cu(II) ions.
KW - Amino Acids
KW - Ascorbic Acid
KW - Benzenesulfonates
KW - Collagen
KW - Collagenases
KW - Copper
KW - Electron Spin Resonance Spectroscopy
KW - Hydrogen Peroxide
KW - Hydroxyl Radical
KW - Iron
KW - Metals
KW - Nitroso Compounds
KW - Oxidants
KW - Oxidation-Reduction
KW - Peptides
KW - Phenylhydrazines
KW - Protein Binding
KW - Spin Trapping
M3 - Journal article
C2 - 9061043
VL - 1360
SP - 84
EP - 96
JO - Biochimica et Biophysica Acta - Reviews on Cancer
JF - Biochimica et Biophysica Acta - Reviews on Cancer
SN - 0304-419X
IS - 1
ER -
ID: 138286087