Hydrogen peroxide dependent oxidative degradation of DNA by copper epinephrine.
The hydrogen peroxide dependent oxidation of the epinephrine-copper complex to adrenochrome is mediated by free copper ions. The oxidation is enhanced by chloride ions and by the presence of serum albumin. The reaction is not inhibited by SOD or by hydroxyl radical scavengers. The 2:1 epinephrine or dopamine:Cu(II) complexes are able to bind to DNA and to catalyze its oxidative destruction in the presence of hydrogen peroxide. The DNA-epinephrine-Cu(II) terenary complex has characteristic spectral properties. It has the capacity to catalyze the reduction of oxygen or H2O2 and it preserves the capacity over a wide range of complex:DNA ratios. The rate of DNA clevage is proportional to the rate of epinephrine oxidation and the rate determining step of the reaction seems to be the reduction of free Cu(II) ions. The ability to form redox active stable DNA ternary complexes, suggests that under specific physiological conditions, when "free" copper ions are available, catecholamines may induce oxidative degradation of DNA and other biological macromolecules.
Aronovitch
J
J
Department of Molecular Biology, School of Medicine, Hebrew University, Jerusalem, Israel.
Godinger
D
D
Czapski
G
G
D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004837:Epinephrine / Q000737:chemistry / Q000494:pharmacology*; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000737:chemistry*; D010084:Oxidation-Reduction; D013053:Spectrophotometry
D005609:Free Radicals; D003300:Copper; D004247:DNA; D006861:Hydrogen Peroxide; D004837:Epinephrine