D-ribosylation induces cognitive impairment through RAGE-dependent astrocytic inflammation

	D-ribosylation induces cognitive impairment through RAGE-dependent astrocytic inflammation
	Han, C.1; Lu, Y.1,2; Wei, Y.1; Wu, B.1,3; Liu, Y.1 ; He, R.1,4
摘要	Non-enzymatic glycation of proteins by reducing saccharides for instance D-glucose is an important post-translational modification regulating protein function. Already two centuries ago, D-glucose (Glc) was identified in the urine of diabetic patients. Recently, abnormally high level of D-ribose (Rib) in the urine of type 2 diabetics has been discovered, which is highly active in protein glycation, resulting in the production of advanced glycation end products (AGEs). Accumulation of AGEs leads to altered cellular function, for example AGE accumulation in the nervous system impairs cognitive ability, yet the mechanisms mediating this process for Rib are unknown. Here we found that treatment with Rib accelerated AGE formation in U251 and U87MG astrocytoma cells and in mouse brain, inducing upregulation of receptor for AGEs (RAGE). Astrocytoma cells with elevated levels of RAGE displayed enhanced activity of the proinflammatory nuclear transcription factor kappaB and increased expression of tumor necrosis factor alpha and glial fibrillary acidic protein. Moreover, injection of Rib induced astrocyte activation in mouse hippocampus and impaired spatial learning and memory abilities. These results indicate that mouse spatial cognitive impairment caused by Rib-derived AGEs is correlated with activation of an astrocyte-mediated, RAGE-dependent inflammatory response. This study may provide insights into the mechanism of Rib-involved cognitive impairments and diabetic encephalopathy.
关键词	advanced glycation end products astrocyte activation D-ribose inflammatory response RAGE type 2 diabetes mellitus
	2014-03-01
语种	英语
发表期刊	CELL DEATH & DISEASE
ISSN	2041-4889
卷号	5 期号:0 页码:e1117
期刊论文类型	Article
收录类别	SCI
WOS记录号	WOS:000333754100021
引用统计	被引频次：42[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.psych.ac.cn/handle/311026/13485
专题	中国科学院心理健康重点实验室
作者单位	1.Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100101, Peoples R China 2.Univ Sci & Technol China, Sch Life Sci, Hefei, Anhui, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China 4.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China
第一作者单位	脑与认知科学国家重点实验室
推荐引用方式 GB/T 7714	Han, C.,Lu, Y.,Wei, Y.,et al. D-ribosylation induces cognitive impairment through RAGE-dependent astrocytic inflammation[J]. CELL DEATH & DISEASE,2014,5(0):e1117.
APA	Han, C.,Lu, Y.,Wei, Y.,Wu, B.,Liu, Y.,&He, R..(2014).D-ribosylation induces cognitive impairment through RAGE-dependent astrocytic inflammation.CELL DEATH & DISEASE,5(0),e1117.
MLA	Han, C.,et al."D-ribosylation induces cognitive impairment through RAGE-dependent astrocytic inflammation".CELL DEATH & DISEASE 5.0(2014):e1117.

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