Polyphenol-induced dissociation of various amyloid fibrils results in a methionine-independent formation of ROS
Polyphenol-induced dissociation of various amyloid fibrils results in a methionine-independent formation of ROS
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DOI：
10.1016/j.bbapap.2008.08.007
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发表时间：
2008-11-01
影响因子：
3.2
通讯作者：
Lichtenberg, Dov
中科院分区：
文献类型：
--
作者：
Shoval, Hila;Weiner, Lev;Lichtenberg, Dov
淀粉样蛋白多肽的纤维化伴随着活性氧物质（ROS）的形成，这进而被认为进一步促进淀粉样蛋白相关的病理。不同的多酚，所有这些都是公认的抗氧化剂，导致淀粉样纤维的解离。本研究涉及后者，了解甚少的过程。具体来说，我们已经调查了六种不同的多酚类物质的A β（42）原纤维的解离，使用电子显微镜和荧光光谱分析。同时，我们已经监测了生产的ROS使用电子自旋共振（ESR）和市售的过氧化物测定试剂盒。使用相同的方法，我们发现姜黄素是A β最有效的去稳定剂之一（42），诱导其他淀粉样多肽[A β（40），A β（42）Nle 35，胰岛淀粉样多肽和α-突触核蛋白片段]的原纤维解离。当溶液中含有痕量的过渡金属时，所有的解离反应都伴随着ROS的形成，与甲硫氨酸残基的存在无关。动力学研究表明，ROS的形成滞后于解离，表明如果这两个过程之间存在因果关系，那么ROS的形成可以被认为是解离的结果而不是原因。这些发现为淀粉样蛋白研究开辟了新的途径，这将需要进一步了解我们的结果及其影响。(C)2008 Elsevier B. V.保留所有权利。
Fibrillization of amyloid polypeptides is accompanied by formation of reactive oxygen species (ROS), which, in turn, is assumed to further promote amyloid-related pathologies. Different polyphenols, all of which are established antioxidants, cause dissociation of amyloid fibrils. This study addresses the latter, poorly understood process. Specifically, we have investigated the dissociation of A beta(42) fibrils by six different polyphenols, using electron microscopy and spectrofluorometric analysis. Simultanously, we have monitored the production of ROS using electron spin resonance (ESR) and the commercially available peroxide assay kit. Using the same methods we found that curcumin, one of the most potent destabilizing agents of A beta(42), induced dissociation of fibrils of other amyloid polypeptides [A beta(40), A beta(42)Nle35, islet amyloid polypeptide and a fragment of alpha-synuclein]. When the solution contained traces of transition metal, all the dissociation reactions were accompanied by ROS formation, independent of the presence of a methionine residue. Kinetic studies show that the formation of ROS lags behind dissociation, indicating that if casual relationship exists between these two processes, then ROS formation may be considered a consequence and not a cause of dissociation. These findings open new avenues in amyloid research that will be required to gain further understanding of our results and of their implications. (C) 2008 Elsevier B.V. All rights reserved.