tailieunhanh - Báo cáo khóa học: Chemical foundation of the attenuation of methylmercury(II) cytotoxicity by metallothioneins

To elucidate the chemical interactions underlying the role of metallothioneins (MTs) in reducing the cytotoxicity caused by MeHg(II), we monitored in parallel by electronic absorption and CDspectroscopies the stepwise addition of MeHgCl stock solution to mammalian Zn7-MT1 and the isolated Zn4 -aMT1 and Zn3 -bMT1 fragments. The incor-poration of MeHg + into Zn7-MT and Zn3-bMT entails total displacement of Zn(II) and unfolding of the protein. However, both features are only partial for Zn4 -aMT. | Eur. J. Biochem. 271 1323-1328 2004 FEBS 2004 doi Chemical foundation of the attenuation of methylmercury II cytotoxicity by metallothioneins Angels Leiva-Presa1 Merce Capdevila1 Neus Cols2 Silvia Atrian2 and Pilar Gonzalez-Duarte1 1 Departament de Quimica Facultat de Ciencies Universitat Autonoma de Barcelona Spain 2Departament de Genetica Facultat de Biologia Universitat de Barcelona Spain To elucidate the chemical interactions underlying the role of metallothioneins MTs in reducing the cytotoxicity caused by MeHg II we monitored in parallel by electronic absorption and CD spectroscopies the ttepwise addíiion of MeHgCl stock solution to mammalian Zn7-MT1 and the isolated Zn4-aMT1 and Zn3-pMT1 fragments. The incorporation of MeHg into Zn7-MT and Zn3-pMT entails total displacement of Zn II and unfolding of the protein. However both features are only partial for Zn4-aMT. The different behavior observed for this fragment whether isolated or constituting one of the two domains of Zn7-MT indicates interdomain interactions in the whole protein. Overall the binding properties of Zn7-MT Zn4-aMT and Zn3-bMT toward MeHg are unprecedented. In addition the sequestration of MeHg by Zn7-MT and the concomitant release of Zn II are probably two of the main contributions in the detoxifying role of mammalian MT. Keywords methylmercury II binding methylmercury II toxicity methylmercury II -metallothionein a-metallothio-nein b-metallothionein. Mercury is a widespread contaminant that enters the environment from a variety of sources including industrial processes and hazardous waste sites. The ability of aquatic micro-organisms to convert metallic mercury into the methylmercury II cation MeHg is the key to its accumulation in fish which then become a common source of exposure of humans to MeHg 1 2 . Whereas the damaging pathological and biochemical consequences of MeHg in humans have long been known current studies are focusing on the effects of MeHg .

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