Reactivity studies of the Fe(III) and Fe(II)NO forms of human neuroglobin reveal a potential role against oxidative stress
Reactivity studies of the Fe(III) and Fe(II)NO forms of human neuroglobin reveal a potential role against oxidative stress
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DOI：
10.1074/jbc.m313732200
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发表时间：
2004-05-28
影响因子：
4.8
通讯作者：
Moens, L
中科院分区：
文献类型：
--
作者：
Herold, S;Fago, A;Moens, L
最近在脊椎动物的大脑和视网膜中发现的神经球蛋白属于六配位球蛋白类，其中远端组氨酸以 Fe(II) 和 Fe(III) 形式与铁中心配位。与大多数其他六配位球蛋白一样，神经球蛋白的生理功能仍不清楚，但似乎与急性缺氧后神经元的存活有关。在这项研究中，我们解决了人类神经红蛋白是否可以充当有毒物质的清除剂的问题，例如一氧化氮、过氧亚硝酸盐和过氧化氢，这些物质在缺氧时大脑中会产生高水平。我们还研究了其 Fe(III) (metNGB) 和 Fe(II)NO 形式与几种试剂的反应动力学。氰化物或NO的结合。 metNGB 遵循双指数动力学，表明存在两种不同的蛋白质构象。在过量 NO 存在的情况下，metNGB 通过还原亚硝基化转化为 NGBFe(II)NO，类似于 NO 的反应。与高铁肌红蛋白和高铁血红蛋白。神经红蛋白的 Fe(II)NO 形式被过氧亚硝酸盐和分子氧氧化为 metNGB，这两个反应也在血红蛋白中发生，尽管速率较低。与肌红蛋白和血红蛋白相反，metNGB在添加过氧亚硝酸盐或过氧化氢后出人意料地不会产生细胞毒性ferry1形式的蛋白质。综上所述，我们的数据表明，人神经红蛋白可能是活性氧化物质的有效清除剂，因此可能在细胞防御氧化应激中发挥作用。
Neuroglobin, recently discovered in the brain and in the retina of vertebrates, belongs to the class of hexaco-ordinate globins, in which the distal histidine coordinates the iron center in both the Fe(II) and Fe(III) forms. As for most other hexacoordinate globins, the physiological function of neuroglobin is still unclear, but seems to be related to neuronal survival following acute hypoxia. In this study, we have addressed the question whether human neuroglobin could act as a scavenger of toxic species, such as nitrogen monoxide, peroxynitrite, and hydrogen peroxide, which are generated at high levels in the brain during hypoxia; we have also investigated the kinetics of the reactions of its Fe(III) (metNGB) and Fe(II)NO forms with several reagents. Binding of cyanide or NO. to metNGB follows bi-exponential kinetics, showing the existence of two different protein conformations. In the presence of excess NO., metNGB is converted into NGBFe(II)NO by reductive nitrosylation, in analogy to the reactions of NO. with metmyoglobin and methemoglobin. The Fe(II)NO form of neuroglobin is oxidized to metNGB by peroxynitrite and dioxygen, two reactions that also take place in hemoglobin, albeit at lower rates. In contrast to myoglobin and hemoglobin, metNGB unexpectedly does not generate the cytotoxic ferryl form of the protein upon addition of either peroxynitrite or hydrogen peroxide. Taken together, our data indicate that human neuroglobin may be an efficient scavenger of reactive oxidizing species and thus may play a role in the cellular defense against oxidative stress.