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Metal specificity in DNA damage prevention by sulfur antioxidants.

Abstract：

:Metals such as CuI and FeII generate hydroxyl radical (.OH) by reducing endogenous hydrogen peroxide (H2O2). Because antioxidants can ameliorate metal-mediated oxidative damage, we have quantified the ability of glutathione, a primary intracellular antioxidant, and other biological sulfur-containing compounds to inhibit metal-mediated DNA damage caused hydroxyl radical. In the CuI/H2O2 system, six sulfur compounds, including both reduced and oxidized glutathione, inhibited DNA damage with IC50 values ranging from 3.4 to 12.4 microM. Glutathione and 3-carboxypropyl disulfide also demonstrated significant antioxidant activity with FeII and H2O2. Additional gel electrophoresis and UV-vis spectroscopy studies confirm that antioxidant activity for sulfur compounds in the CuI system is attributed to metal coordination, a previously unexplored mechanism. The antioxidant mechanism for sulfur compounds in the FeII system, however, is unlike that of CuI. Our results demonstrate that glutathione and other sulfur compounds are potent antioxidants capable of preventing metal-mediated oxidative DNA damage at well below their biological concentrations. This novel metal-binding antioxidant mechanism may play a significant role in the antioxidant behavior of these sulfur compounds and help refine understanding of glutathione function in vivo.

journal_name

J Inorg Biochem

journal_title

Journal of inorganic biochemistry

authors

Battin EE,Brumaghim JL

doi

10.1016/j.jinorgbio.2008.06.010

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

2036-42

issue

12

eissn

0162-0134

issn

1873-3344

pii

S0162-0134(08)00150-5

journal_volume

102

pub_type

杂志文章

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