Myricetin Inhibits Islet Amyloid Polypeptide (IAPP) Aggregation and Rescues Living Mammalian Cells from IAPP Toxicity.
Myricetin Inhibits Islet Amyloid Polypeptide (IAPP) Aggregation and Rescues Living Mammalian Cells from IAPP Toxicity.
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DOI：
10.2174/1874091x01206010066
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Moffet DA
中科院分区：
文献类型：
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作者：
Zelus C;Fox A;Calciano A;Faridian BS;Nogaj LA;Moffet DA
淀粉样蛋白生成多肽IAPP（胰岛淀粉样多肽，胰淀素）的聚集被认为在II型糖尿病中胰岛β细胞的死亡中起直接作用。预防IAPP的初始聚集事件是减缓并可能预防这种疾病进展的一种策略。在这里，我们研究了杨梅素作为IAPP聚集抑制剂的潜力。我们发现，杨梅素阻止硫磺素T结合的浓度依赖性的方式。原子力显微镜显示，杨梅素防止纤维形成在严格的条件下有利于形成IAPP聚集体。使用IAPP-EGFP（增强型绿色荧光蛋白）蛋白构建体，我们发现高浓度的杨梅素减缓了IAPP-EGFP的体内聚集。还发现杨梅素可以拯救活的哺乳动物细胞免受IAPP的毒性作用。这些结果表明，杨梅素是IAPP淀粉样蛋白聚集的强抑制剂，并且是开发淀粉样蛋白抑制治疗剂的潜在先导分子。
The aggregation of the amyloidogenic polypeptide IAPP (Islet Amyloid Polypeptide, amylin) is believed to play a direct role in the death of pancreatic β-islet cells in type II diabetes. Preventing the initial aggregation event of IAPP is one strategy for slowing, and possibly preventing, the progression of this disease. Here, we investigate myricetin’s potential as an inhibitor of IAPP aggregation. We show that myricetin prevented thioflavin T binding in a concentration dependent manner. Atomic force microscopy revealed that myricetin prevented fiber formation under rigorous conditions conducive to forming IAPP aggregates. Using an IAPP-EGFP (Enhanced Green Fluorescent Protein) protein construct, we find that high concentrations of myricetin slowed the in vivo aggregation of IAPP-EGFP. Myricetin was also found to rescue living mammalian cells from the toxic effects of IAPP. These results indicate that myricetin is a strong inhibitor of IAPP amyloid aggregation and a potential lead molecule for the development of an amyloid inhibiting therapeutic.