Ferritin with methylglyoxal produces reactive oxygen species but remains functional.

IF 3.6 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Adriana Rybnikářová, Richard Buchal, Jan Pláteník
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引用次数: 0

Abstract

Iron is necessary for life, but the simultaneous iron-catalyzed formation of reactive oxygen species (ROS) is involved in pathogenesis of many diseases. One of them is diabetes mellitus, a widespread disease with severe long-term complications, including neuropathy, retinopathy, and nephropathy. Much evidence points to methylglyoxal, a potent glycating agent, as the key mediator of diabetic complications. In diabetes, there is also a peculiar dysregulation of iron homeostasis, leading to an expansion of redox-active iron. This in vitro study focuses on the interaction of methylglyoxal with ferritin, which is the main cellular protein for iron storage. Methylglyoxal effectively liberates iron from horse spleen ferritin, as well as synthetic iron cores; in both cases, it is partially mediated by superoxide. The interaction of methylglyoxal with ferritin increases the production of hydrogen peroxide, much above the generation of peroxide by methylglyoxal alone, in an iron-dependent manner. Glycation with methylglyoxal results in structural changes in ferritin. All of these findings can be demonstrated with pathophysiologically relevant (submillimolar) methylglyoxal concentrations. However, the rate of iron release by ascorbate, the ferroxidase activity, or the diameter of gated pores even in intensely glycated ferritin is not altered. In conclusion, although the functional features of ferritin resist alterations due to glycation, the interaction of methylglyoxal with ferritin liberates iron and markedly increases ROS production, both of which could enhance oxidative stress in vivo. Our findings may have implications for the pathogenesis of long-term diabetic complications, as well as for the use of ferritin as a nanocarrier in chemotherapy.

含有甲基乙二醛的铁蛋白会产生活性氧,但仍能发挥作用。
铁是生命所必需的,但同时由铁催化形成的活性氧(ROS)与许多疾病的发病机制有关。其中之一就是糖尿病,这是一种广泛存在的疾病,具有严重的长期并发症,包括神经病变、视网膜病变和肾病。许多证据表明,强效糖化剂甲基乙二酸是糖尿病并发症的关键介质。糖尿病患者体内的铁平衡失调,导致氧化还原活性铁增加。这项体外研究的重点是甲基乙二酸与铁蛋白的相互作用,铁蛋白是储存铁的主要细胞蛋白。甲基乙二醛能有效地从马脾脏铁蛋白和合成铁核中释放铁;在这两种情况下,其部分作用都是由超氧化物介导的。甲基乙二醛与铁蛋白的相互作用增加了过氧化氢的产生,远远高于甲基乙二醛单独产生的过氧化氢,其产生方式与铁有关。甲基乙二醛的糖化作用导致铁蛋白的结构发生变化。所有这些发现都可以用病理生理相关(亚毫摩尔)浓度的甲基乙二醛来证明。然而,抗坏血酸释放铁的速率、铁氧化酶的活性或门控孔的直径,即使在强烈糖化的铁蛋白中也没有改变。总之,虽然铁蛋白的功能特征不会因糖化而改变,但甲基乙二酸与铁蛋白的相互作用会释放铁并显著增加 ROS 的产生,这两者都会增强体内的氧化应激。我们的发现可能对长期糖尿病并发症的发病机制以及将铁蛋白用作化疗中的纳米载体有影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Free Radical Research
Free Radical Research 生物-生化与分子生物学
CiteScore
6.70
自引率
0.00%
发文量
47
审稿时长
3 months
期刊介绍: Free Radical Research publishes high-quality research papers, hypotheses and reviews in free radicals and other reactive species in biological, clinical, environmental and other systems; redox signalling; antioxidants, including diet-derived antioxidants and other relevant aspects of human nutrition; and oxidative damage, mechanisms and measurement.
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