Combined Effects of Manganese, Iron, Copper, and Dopamine on Oxidative DNA Damage

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概要

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• Manganese (Mn) damages the central nervous system and causes Parkinsons disease (PD)-like syndrome called manganism. Abnormal accumulation of Mn and iron (Fe) is observed in the basal nuclei of patients with PD. Dopamine induces oxidative DNA damage in the presence of Fe or copper (Cu) in vitro. Therefore, an Mn-induced neural disorder may involve combined actions of Mn, Fe/Cu, and catecholamines. Here we investigated the combined effects of Mn(II) on the DNA damage induced by dopamine and either Fe(III) or Cu(II). Mn(II) enhanced the formation of 7,8-dihydro-8-oxo-2-deoxyguanosine (8-oxodG) induced by dopamine and Fe(III)/Cu(II), whereas Mn(II) did not induce 8-oxodG formation in the absence of Fe(III)/Cu(II). Mn(II) accelerated hydrogen peroxide (H2O2) production in the dopamine-Fe(III)/Cu(II) system. Furthermore, Mn(II) decreased superoxide anion radicals (O2•-) generated in the xanthine-xanthine oxidase system. These results indicate that Mn(II)-mediated enhancement of DNA damage is caused by facilitated conversion of O2•- to H2O2. In addition, Mn(II) accelerated the formation of aminochrome, an oxidized dopamine product, in the presence of Cu(II). This reaction may have involved Mn(III) accompanied by H2O2 production from O2•-, suggesting a mechanism for Mn-induced oxidative stress on dopaminergic neurons through the combined actions of Mn, Fe, Cu, and dopamine.

• 公益社団法人　日本薬学会の論文

著者

• Ando Motozumi

  Faculty of Pharmacy, Meijo University

• Ueda Koji

  Faculty of Pharmacy, Meijo University

• Okamoto Yoshinori

  Faculty of Pharmacy, Meijo University

• Kojima Nakao

  Faculty of Pharmacy, Meijo University

• Kojima Nakao

  Faculty Of Pharmacy Meijo University

• Okamoto Yoshinori

  Fac. Of Pharmacy Meijo Univ.

• UEDA Koji

  Faculty of Agriculture, Yamagata University

• Kojima Nakao

  Faculty of Pharmaceutical Sciences, Kyoto University

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