Comparison of iron-catalyzed DNA and lipid oxidation.
Lipid and DNA oxidation catalyzed by iron(II) were compared in HEPES and phosphate buffers. Lipid peroxidation was examined in a sensitive liposome system constructed with a fluorescent probe that allowed us to examine the effects of both low and high iron concentrations. With liposomes made from synthetic 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine or from rat liver microsomal lipid, lipid peroxidation increased with iron concentration up to the range of 10--20 microM iron(II), but then rates decreased with further increases in iron concentration. This may be due to the limited amount of lipid peroxides available in liposomes for oxidation of iron(II) to generate equimolar iron(III), which is thought to be important for the initation of lipid peroxidation. Addition of hydrogen peroxide to incubations with 1--10 microM iron(II) decreased rates of lipid peroxidation, whereas addition of hydrogen peroxide to incubations with higher iron concentrations increased rates of lipid peroxidation. Thus, in this liposome system, sufficient peroxide from either within the lipid or from exogenous sources must be present to generate equimolar iron(II) and iron(III). With iron-catalyzed DNA oxidation, hydrogen peroxide always stimulated product formation. Phosphate buffer, which chelates iron but still allows for generation of hydroxyl radicals, inhibited lipid peroxidation but not DNA oxidation. HEPES buffer, which scavenges hydroxyl radicals, inhibited DNA oxidation, whereas lipid peroxidation was unaffected since presumably iron(II) and iron(III) were still available for reaction with liposomes in HEPES buffer.
Djuric
Z
Z
Barbara Ann Karmanos Cancer Institute, 110 East Warren, Detroit, MI, USA. Djuricz@karamanos.org
Potter
D W
DW
Taffe
B G
BG
Strasburg
G M
GM
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D004247:DNA / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D005290:Ferric Compounds / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000032:analysis; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007501:Iron / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000378:metabolism; D007700:Kinetics; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008081:Liposomes; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013936:Thymidine / Q000031:analogs & derivatives / Q000032:analysis
D005290:Ferric Compounds; D005296:Ferrous Compounds; D005456:Fluorescent Dyes; D007502:Iron Chelating Agents; D008054:Lipid Peroxides; D008081:Liposomes; C018080:5-hydroxymethyl-2'-deoxyuridine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D006861:Hydrogen Peroxide; D007501:Iron; D003849:Deoxyguanosine; D013936:Thymidine