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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
Source PublicationCELL DEATH & DISEASE
AbstractNon-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.
Keywordadvanced glycation end products astrocyte activation D-ribose inflammatory response RAGE type 2 diabetes mellitus
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WOS IDWOS:000333754100021
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Document Type期刊论文
Affiliation1.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
Recommended Citation
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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