期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 66, 期 15, 页码 2559-2571出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-009-0058-7
关键词
D-Ribose; Tau protein; Glycation; Aggregation; Cytotoxicity
资金
- NSFB [06J11]
- NSFC [30621004]
- 973-project [2006CB500703]
- CAS [KSCX2-YW-R-119]
Although the glycation of Tau that is involved in paired helical filament formation in Alzheimer's disease has been widely studied, little attention has been paid to the role of d-ribose in the glycation of Tau. Here, we show that Tau is rapidly glycated in the presence of d-ribose, resulting in oligomerization and polymerization. Glycated derivatives appeared after 24 h incubation. Western blotting indicated the formation of advanced glycation end-products (AGEs) during initial stages of glycation. Thioflavin T-positive (ThT-positive) aggregations that appeared from day 4 indicated the globular-like features. Atomic force microscopy revealed that the surface morphology of ribosylated Tau40 was globular-like. Kinetic studies suggested that d-ribosylated Tau is slowly oligomerized and rapidly polymerized with ThT-positive features. Moreover, d-ribosylated Tau aggregates were highly toxic to SHSY5Y cells and resulted in both apoptosis and necrosis. This work has demonstrated that d-ribose reacted with Tau protein rapidly, producing ThT-positive aggregations which had high cytotoxicity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据