ZINC AND ALZHEIMERS-DISEASE - RESPONSE
ZINC AND ALZHEIMERS-DISEASE - RESPONSE
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DOI：
10.1126/science.268.5219.1921
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发表时间：
1995-06-30
期刊：
影响因子：
56.9
通讯作者：
TANZI, RE
中科院分区：
文献类型：
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作者：
BUSH, AI;MOIR, RD;TANZI, RE
结果表明，我们的实验(1)是一个低于镁、钙、铜和铁的生理浓度(3千米)的浓度。我们通过研究生物体液中金属离子的最大总浓度来解决这个问题(表2)。我们的数据表明，Ca(II)和Mg(II)在1 mm处，Fe(III)在25 PM(表1和2)时，在过滤分析中不会显著地诱导A13-40的保留。Cu(Ii)在25岁[.M使滤液中OD214损失20%，Fe(II)在-8时损失40%(表2)，这些结果证实了25，um Fe(II)对A13I40溶解度的影响与相同浓度的Zn(II)相同(2)。为了表征这一反应，我们将API 40与EDTA、锌(II)或铁(II)孵育，并通过免疫印迹和刚果红染色检测离心后小球的含量。蛋白质免疫印迹分析证实，只有当多肽与锌(II)在-8微米孵育时，才能产生丰富的API 40沉淀(图2)。Fe(II)诱导的Al_(40)沉淀数量少得多，在显微镜下观察到稀疏的未着色颗粒，其平均尺寸比锌诱导的小得多。相反，锌导致大量颗粒的形成，这些颗粒在光学显微镜下可见，通常直径达10-40PLM，并被刚果红染色(1)。这些观察结果得到了滤液、滤液蛋白印迹和离心上清液的OD214测定(数据未显示)的证实。观察到Al_(40)与Fe(II)孵育后的过滤滞留超过了球团形成，表明Fe(II)诱导的反应产物与锌(II)诱导的反应产物有显著的质的差异。
c., zy ing out that our experiments (1) were con-ducted ata concentration (3 KM) that is lower than the physiological concentrations of Mg, Ca, Cu, and Fe. We have addressed this question by performing studies of the effects of metal ions at the maximum total concentrations at which they are found in biological fluids (Table 2). Out data indicate that Ca (II) and Mg (II) at 1 mM, and Fe (III) at 25 pM (Tables1 and 2), do not significantly induce retention of A13 40 in the filtration assay. Cu (II) at 25 [. M in-duces a 20% loss of OD214 in the filtrate, and Fe (II) at-8 pM induces a 40% loss (Table 2).These findings confirm that the effect of 25, uM Fe (II) on A13I40 solubility resem-bles that of Zn (II) at the same concentration (2). To characterize this reaction, we incubated API 40 with EDTA, Zn (II), or Fe (II) and examined the content of the pellets after centrifugation by immunoblot and Congo Red staining. Protein immu-noblot analysis confirmed that abundant API 40 precipitate was produced only when the peptide was incubated with Zn (II) at-8, uM (Fig. 2). A much smaller amount of AI40 precipitate was induced by Fe (II), and sparse unstained particles, of much smaller averagesize than those induced by Zn, were observed under the microscope in the resuspended pellet. In contrast, Zn in-duces the formation of abundant particles that are visible by light microscopy, fre-quently as large as 10 to 40 pLm in diameter, and stained by Congo Red (1). These ob-servations were corroboratedby capture ELISA assay of thefiltrates, proteinimmu-noblots of the filter retentates, and by OD214 measurements of the centrifuged su-pernatants (data not shown). The observa-tion that filter retention of AI_40 exceeded pellet formation after incubation with Fe (II) indicates that there are significant qualitative differences between the reaction products induced by Fe (II) as opposed to Zn (II).