Copper catalyzed oxidation of Alzheimer Abeta.
Copper catalyzed oxidation of Alzheimer Abeta.
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DOI：
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发表时间：
2000-06
影响因子：
1.6
通讯作者：
C. Atwood;X. Huang;A. Khatri;R. Scarpa;Y. S. Kim;R. Moir;R. Tanzi;A. Roher;A. Bush
中科院分区：
文献类型：
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作者：
C. Atwood;X. Huang;A. Khatri;R. Scarpa;Y. S. Kim;R. Moir;R. Tanzi;A. Roher;A. Bush
来自阿尔茨海默病患者大脑淀粉样斑块的Aβ含有几种氧化翻译后修饰。在这项研究中，我们表征了人淀粉样蛋白来源的Abeta的氨基酸含量，并与金属催化氧化的人合成Abeta的氨基酸含量进行了比较。与预期的氨基酸含量相比，人淀粉样蛋白Abeta的精氨酸(46%)和谷氨酸/谷氨酰胺残基(28%)含量增加，但组氨酸残基含量(-32%)降低。在H_2O_2存在下，合成的人Abeta与铜(II)孵育，但不与Fe(III)孵育，同样引起组氨酸残基的减少(-79%)，但酪氨酸残基的减少(-28%)。我们的结果表明，组氨酸和酪氨酸最容易受到金属介导的氧化攻击，这与我们早期的发现一致，即铜通过组氨酸残基配位具有氧化还原能力。我们的结果表明，人类淀粉样蛋白来源的Abeta中组氨酸残基的丢失可能是铜氧化的结果，而且在体内，未知的翻译后机制作用于Abeta的其他氨基酸。
Abeta derived from amyloid plaques of Alzheimer's disease-affected brain contain several oxidative posttranslational modifications. In this study we have characterized the amino acid content of human amyloid-derived Abeta and compared it with that of human synthetic Abeta subjected to metal-catalyzed oxidation. Human amyloid derived Abeta has an increased content of arginine (46%) and glutamate/glutamine residues (28%), but a decreased content of histidine residues (-32%) as compared to the expected amino acid content. Incubation of synthetic human Abeta with Cu(II), but not Fe(III), in the presence of H2O2 similarly induced a decrease in histidine residues (-79%), but also a decrease in tyrosine residues (-28%). Our results suggest that histidine and tyrosine are most vulnerable to metal mediated oxidative attack, consistent with our earlier findings that Cu coordinated via histidine residues is redox competent. Our results suggest that the loss of histidine residues in human amyloid-derived Abeta may be a result of Cu oxidation, and that unidentified post-translational mechanisms operate to modify other amino acids of Abeta in vivo.