Oxidation of DNA, proteins and lipids by DOPA, protein-bound DOPA, and related catechol(amine)s

TY - JOUR

T1 - Oxidation of DNA, proteins and lipids by DOPA, protein-bound DOPA, and related catechol(amine)s

AU - Pattison, David I

AU - Dean, Roger T

AU - Davies, Michael Jonathan

PY - 2002/8/1

Y1 - 2002/8/1

N2 - Incubation of free 3,4-dihydroxyphenylalanine (DOPA), protein-bound DOPA (PB-DOPA) and related catechols with DNA, proteins and lipids has been shown to result in oxidative damage to the target molecule. This article reviews these reactions with particular emphasis on those that occur in the presence of molecular O(2) and redox-active metal ions (e.g. Fe(3+), Cu(2+), Cr(6+)), which are known to increase the rate of DOPA oxidation. The majority of oxidative damage appears to be mediated by reactive oxygen species (ROS) such as superoxide and HO(.) radicals, though other DOPA oxidation products, including semiquinone radicals, quinones, and metal ion-DOPA complexes have also been implicated in some cases. Non-radical reactions of DOPA with suitable nucleophiles (e.g. thiol groups) can also result in modification of the target, with this process being particularly prevalent with proteins. The exacerbation of damage observed on addition of H(2)O(2) is in accord with a key role for ROS in many of these reactions.

AB - Incubation of free 3,4-dihydroxyphenylalanine (DOPA), protein-bound DOPA (PB-DOPA) and related catechols with DNA, proteins and lipids has been shown to result in oxidative damage to the target molecule. This article reviews these reactions with particular emphasis on those that occur in the presence of molecular O(2) and redox-active metal ions (e.g. Fe(3+), Cu(2+), Cr(6+)), which are known to increase the rate of DOPA oxidation. The majority of oxidative damage appears to be mediated by reactive oxygen species (ROS) such as superoxide and HO(.) radicals, though other DOPA oxidation products, including semiquinone radicals, quinones, and metal ion-DOPA complexes have also been implicated in some cases. Non-radical reactions of DOPA with suitable nucleophiles (e.g. thiol groups) can also result in modification of the target, with this process being particularly prevalent with proteins. The exacerbation of damage observed on addition of H(2)O(2) is in accord with a key role for ROS in many of these reactions.

KW - Animals

KW - Catecholamines

KW - DNA

KW - DNA Damage

KW - Dihydroxyphenylalanine

KW - Humans

KW - Lipid Metabolism

KW - Lipid Peroxidation

KW - Oxidation-Reduction

KW - Protein Binding

KW - Proteins

KW - Reactive Oxygen Species

M3 - Journal article

C2 - 12126793

SN - 0300-483X

VL - 177

SP - 23

EP - 37

JO - Toxicology

JF - Toxicology

IS - 1

ER -