The protein oxidation product 3,4-dihydroxyphenylalanine (DOPA) mediates oxidative DNA damage
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The protein oxidation product 3,4-dihydroxyphenylalanine (DOPA) mediates oxidative DNA damage. / Morin, B; Davies, Michael Jonathan; Dean, R T.
In: Biochemical Journal, Vol. 330 ( Pt 3), 15.03.1998, p. 1059-67.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The protein oxidation product 3,4-dihydroxyphenylalanine (DOPA) mediates oxidative DNA damage
AU - Morin, B
AU - Davies, Michael Jonathan
AU - Dean, R T
PY - 1998/3/15
Y1 - 1998/3/15
N2 - A major product of hydroxy-radical addition to tyrosine is 3, 4-dihydroxyphenylalanine (DOPA) which has reducing properties. Protein-bound DOPA (PB-DOPA) has been shown to be a major component of the stable reducing species formed during protein oxidation under several conditions. The aim of the present work was to investigate whether DOPA, and especially PB-DOPA, can mediate oxidative damage to DNA. We chose to generate PB-DOPA using mushroom tyrosinase, which catalyses the hydroxylation of tyrosine residues in protein. This permitted us to study the reactions of PB-DOPA in the virtual absence of other protein-bound oxidation products. The formation of two oxidation products of DNA, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodG) and 5-hydroxy-2'-deoxycytidine (5OHdC), were studied with a novel HPLC using gradient elution and an electrochemical detection method, which allowed the detection of both DNA modifications in a single experiment. We found that exposure of calf thymus DNA to DOPA or PB-DOPA resulted in the formation of 8oxodG and 5OHdC, with the former predominating. The formation of these DNA oxidation products by either DOPA or PB-DOPA depended on the presence of oxygen, and also on the presence and on the concentration of transition metal ions, with copper being more effective than iron. The yields of 8oxodG and 5OHdC increased with DOPA concentration in proteins. Thus PB-DOPA was able to promote further radical-generating events, which then transferred damage to other biomolecules such as DNA.
AB - A major product of hydroxy-radical addition to tyrosine is 3, 4-dihydroxyphenylalanine (DOPA) which has reducing properties. Protein-bound DOPA (PB-DOPA) has been shown to be a major component of the stable reducing species formed during protein oxidation under several conditions. The aim of the present work was to investigate whether DOPA, and especially PB-DOPA, can mediate oxidative damage to DNA. We chose to generate PB-DOPA using mushroom tyrosinase, which catalyses the hydroxylation of tyrosine residues in protein. This permitted us to study the reactions of PB-DOPA in the virtual absence of other protein-bound oxidation products. The formation of two oxidation products of DNA, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodG) and 5-hydroxy-2'-deoxycytidine (5OHdC), were studied with a novel HPLC using gradient elution and an electrochemical detection method, which allowed the detection of both DNA modifications in a single experiment. We found that exposure of calf thymus DNA to DOPA or PB-DOPA resulted in the formation of 8oxodG and 5OHdC, with the former predominating. The formation of these DNA oxidation products by either DOPA or PB-DOPA depended on the presence of oxygen, and also on the presence and on the concentration of transition metal ions, with copper being more effective than iron. The yields of 8oxodG and 5OHdC increased with DOPA concentration in proteins. Thus PB-DOPA was able to promote further radical-generating events, which then transferred damage to other biomolecules such as DNA.
KW - Basidiomycota
KW - Cobalt Radioisotopes
KW - Copper
KW - DNA
KW - DNA Damage
KW - Dihydroxyphenylalanine
KW - Electron Spin Resonance Spectroscopy
KW - Gamma Rays
KW - Insulin
KW - Kinetics
KW - Monophenol Monooxygenase
KW - Oxidation-Reduction
KW - Proteins
KW - Serum Albumin, Bovine
M3 - Journal article
C2 - 9494069
VL - 330 ( Pt 3)
SP - 1059
EP - 1067
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
ER -
ID: 138284521