Muroran Institute of Technology, Graduate School of Engineering, Muroran 050-8585, Japan.
Research Center of Global Agromedicine, Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan.
Int J Mol Sci. 2021 Jan 21;22(3):1036. doi: 10.3390/ijms22031036.
Amyloid A (AA) amyloidosis is a condition in which amyloid fibrils characterized by a linear morphology and a cross-β structure accumulate and are deposited extracellularly in organs, resulting in chronic inflammatory diseases and infections. The incidence of AA amyloidosis is high in humans and several animal species. Serum amyloid A (SAA) is one of the most important precursor amyloid proteins and plays a vital step in AA amyloidosis. Amyloid enhancing factor (AEF) serves as a seed for fibril formation and shortens the onset of AA amyloidosis sharply. In this study, we examined whether AEFs extracted and purified from five animal species (camel, cat, cattle, goat, and mouse) could promote mouse SAA (mSAA) protein aggregation in vitro using quantum-dot (QD) nanoprobes to visualize the aggregation. The results showed that AEFs shortened and promoted mSAA aggregation. In addition, mouse and cat AEFs showed higher mSAA aggregation-promoting activity than the camel, cattle, and goat AEFs. Interestingly, homology analysis of SAA in these five animal species revealed a more similar amino acid sequence homology between mouse and cat than between other animal species. Furthermore, a detailed comparison of amino acid sequences suggested that it was important to mSAA aggregation-promoting activity that the 48th amino acid was a basic residue (Lys) and the 125th amino acid was an acidic residue (Asp or Glu). These data imply that AA amyloidosis exhibits higher transmission activity among animals carrying genetically homologous SAA gene, and may provide a new understanding of the pathogenesis of amyloidosis.
淀粉样 A (AA) 淀粉样变性是一种疾病，其特征是具有线性形态和交叉-β结构的淀粉样纤维积累并在器官中外泌体沉积，导致慢性炎症性疾病和感染。AA 淀粉样变性在人类和几种动物物种中的发病率很高。血清淀粉样蛋白 A (SAA) 是最重要的淀粉样前体蛋白之一，在 AA 淀粉样变性中起着至关重要的作用。淀粉样增强因子 (AEF) 作为纤维形成的种子，可急剧缩短 AA 淀粉样变性的发病时间。在这项研究中，我们使用量子点 (QD) 纳米探针检查了从五种动物物种（骆驼、猫、牛、山羊和小鼠）中提取和纯化的 AEF 是否可以促进体外小鼠 SAA (mSAA) 蛋白聚集，以可视化聚集。结果表明 AEF 缩短并促进 mSAA 聚集。此外，小鼠和猫 AEF 比骆驼、牛和山羊 AEF 显示出更高的 mSAA 聚集促进活性。有趣的是，这五种动物物种 SAA 的同源性分析表明，小鼠和猫之间的氨基酸序列同源性比其他动物物种之间更相似。此外，对氨基酸序列的详细比较表明，第 48 位氨基酸为碱性残基（Lys），第 125 位氨基酸为酸性残基（Asp 或 Glu）对 mSAA 聚集促进活性很重要。这些数据表明，携带遗传同源 SAA 基因的动物中 AA 淀粉样变性表现出更高的传播活性，可能为淀粉样变性的发病机制提供新的认识。
