Iron(II) and Hydrogen Peroxide Detoxification by Human H-Chain Ferritin. An EPR Spin-Trapping Study
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- 作者：Guanghua Zhao ; Paolo Arosio ; and N. Dennis Chasteen
- 刊名：Biochemistry
- 出版年：2006
- 出版时间：March 14, 2006
- 年：2006
- 卷：45
- 期：10
- 页码：3429 - 3436
- 全文大小：105K
- 年卷期：v.45,no.10(March 14, 2006)
- ISSN：1520-4995
文摘
Overexpression of human H-chain ferritin (HuHF) is known to impart a degree of protectionto cells against oxidative stress and the associated damage to DNA and other cellular components. However,whether this protective activity resides in the protein's ability to inhibit Fenton chemistry as found forDps proteins has never been established. Such inhibition does not occur with the related mitochondrialferritin which displays much of the same iron chemistry as HuHF, including an Fe(II)/H2O2 oxidationstoichiometry of ~2:1. In the present study, the ability of HuHF to attenuate hydroxyl radical productionby the Fenton reaction (Fe2+ + H2O2 
Fe3+ + OH- + ·OH) was examined by electron paramagneticresonance (EPR) spin-trapping methods. The data demonstrate that the presence of wild-type HuHF duringFe2+ oxidation by H2O2 greatly decreases the amount of ·OH radical produced from Fenton chemistrywhereas the ferroxidase site mutant 222 (H62K + H65G) and human L-chain ferritin (HuLF) lack thisactivity. HuHF catalyzes the pairwise oxidation of Fe2+ by the detoxification reaction [2Fe2+ + H2O2 +2H2O 2Fe(O)OHcore + 4H+] that occurs at the ferroxidase site of the protein, thereby preventing theproduction of hydroxyl radical. The small amount of ·OH radical that is produced in the presence offerritin (
1% of the iron oxidized) appears to arise from the reaction of H2O2 with Fe(III) in the proteinrather than from simple Fenton chemistry. The results are discussed in terms of recent experiments reportingboth protective and degradative effects of ferritin iron on the integrity of nuclear DNA.
Fe3+ + OH- + ·OH) was examined by electron paramagneticresonance (EPR) spin-trapping methods. The data demonstrate that the presence of wild-type HuHF duringFe2+ oxidation by H2O2 greatly decreases the amount of ·OH radical produced from Fenton chemistrywhereas the ferroxidase site mutant 222 (H62K + H65G) and human L-chain ferritin (HuLF) lack thisactivity. HuHF catalyzes the pairwise oxidation of Fe2+ by the detoxification reaction [2Fe2+ + H2O2 +2H2O 2Fe(O)OHcore + 4H+] that occurs at the ferroxidase site of the protein, thereby preventing theproduction of hydroxyl radical. The small amount of ·OH radical that is produced in the presence offerritin (1% of the iron oxidized) appears to arise from the reaction of H2O2 with Fe(III) in the proteinrather than from simple Fenton chemistry. The results are discussed in terms of recent experiments reportingboth protective and degradative effects of ferritin iron on the integrity of nuclear DNA.