Biomaterial Database

Glutathione/Fe3+/O2-mediated DNA strand breaks and 8-hydroxydeoxyguanosine formation. Enhancement by copper, zinc superoxide dismutase. 1997

J W Park, and R A Floyd

Department of Biochemistry, Kyungpook National University, Taegu, South Korea. parkjw@bh.kyungpook.ac.kr

Oxidative DNA damage reflected by the formation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and strand breaks caused by a glutathione mixed-function oxidation system (GSH-MFO) comprised of Fe3+, O2, and glutathione as an electron donor was enhanced by copper, zinc superoxide dismutase (CuZnSOD) in a concentration-dependent manner. Unlike CuZnSOD, manganese SOD (MnSOD) as well as iron SOD (FeSOD) did not enhance either strand breaks or 8-OH-dH formation in DNA. The capacity of CuZnSOD to enhance damage to DNA was inhibited by 5,5-dimethyl-1-pyrroline N-oxide (DMPO), a spin trapping agent. The salicylate hydroxylation assay showed that hydroxyl radicals formed in the presence of the GSH-MFO system was increased by CuZnSOD. The GSH-MFO system caused the release of free copper from CuZnSOD. Based on these results, we interpret the effects of CuZnSOD on the GSH-MFO induced DNA damage as due to reactive oxygen species, probably .OH, formed by the reaction of free Cu2+, released from oxidatively damaged CuZnSOD, and H2O2 produced by the GSH-MFO system.

UI	MeSH Term	Description	Entries
D010100	Oxygen	An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.	Dioxygen,Oxygen-16,Oxygen 16
D003849	Deoxyguanosine	A nucleoside consisting of the base guanine and the sugar deoxyribose.
D004249	DNA Damage	Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.	DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D005290	Ferric Compounds	Inorganic or organic compounds containing trivalent iron.	Compounds, Ferric
D005978	Glutathione	A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.	Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D006899	Mixed Function Oxygenases	Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.	Hydroxylase,Hydroxylases,Mixed Function Oxidase,Mixed Function Oxygenase,Monooxygenase,Monooxygenases,Mixed Function Oxidases,Function Oxidase, Mixed,Function Oxygenase, Mixed,Oxidase, Mixed Function,Oxidases, Mixed Function,Oxygenase, Mixed Function,Oxygenases, Mixed Function
D000080242	8-Hydroxy-2'-Deoxyguanosine	Common oxidized form of deoxyguanosine in which C-8 position of guanine base has a carbonyl group.	2'-Deoxy-7,8-Dihydro-8-Oxoguanosine,2'-Deoxy-8-Hydroxyguanosine,2'-Deoxy-8-Oxo-7,8-Dihydroguanosine,2'-Deoxy-8-Oxoguanosine,7,8-Dihydro-8-Oxo-2'-Deoxyguanosine,7-Hydro-8-Oxodeoxyguanosine,8-Hydroxydeoxyguanosine,8-Oxo-2'-Deoxyguanosine,8-Oxo-7,8-Dihydro-2'-Deoxyguanosine,8-Oxo-7,8-Dihydrodeoxyguanosine,8-Oxo-7-Hydrodeoxyguanosine,8-Oxo-Deoxyguanosine,8OHdG,8-OH-dG,8-oxo-dG,8-oxo-dGuo,8-oxodG,8-oxodGuo,2' Deoxy 7,8 Dihydro 8 Oxoguanosine,2' Deoxy 8 Hydroxyguanosine,2' Deoxy 8 Oxo 7,8 Dihydroguanosine,2' Deoxy 8 Oxoguanosine,7 Hydro 8 Oxodeoxyguanosine,7,8 Dihydro 8 Oxo 2' Deoxyguanosine,8 Hydroxy 2' Deoxyguanosine,8 Hydroxydeoxyguanosine,8 Oxo 2' Deoxyguanosine,8 Oxo 7 Hydrodeoxyguanosine,8 Oxo 7,8 Dihydro 2' Deoxyguanosine,8 Oxo 7,8 Dihydrodeoxyguanosine,8 Oxo Deoxyguanosine
D013482	Superoxide Dismutase	An oxidoreductase that catalyzes the reaction between SUPEROXIDES and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide.	Hemocuprein,Ag-Zn Superoxide Dismutase,Cobalt Superoxide Dismutase,Cu-Superoxide Dismutase,Erythrocuprein,Fe-Superoxide Dismutase,Fe-Zn Superoxide Dismutase,Iron Superoxide Dismutase,Manganese Superoxide Dismutase,Mn-SOD,Mn-Superoxide Dismutase,Ag Zn Superoxide Dismutase,Cu Superoxide Dismutase,Dismutase, Ag-Zn Superoxide,Dismutase, Cobalt Superoxide,Dismutase, Cu-Superoxide,Dismutase, Fe-Superoxide,Dismutase, Fe-Zn Superoxide,Dismutase, Iron Superoxide,Dismutase, Manganese Superoxide,Dismutase, Mn-Superoxide,Dismutase, Superoxide,Fe Superoxide Dismutase,Fe Zn Superoxide Dismutase,Mn SOD,Mn Superoxide Dismutase,Superoxide Dismutase, Ag-Zn,Superoxide Dismutase, Cobalt,Superoxide Dismutase, Fe-Zn,Superoxide Dismutase, Iron,Superoxide Dismutase, Manganese