Abstract
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.
Highlights
The roles of Rib in glycation and its resulting effects in vitro and in vivo have drawn increased attention in recent years.[3]
Rib induced astrocyte activation in mouse hippocampus and impaired spatial learning and memory ability. These results suggest that mouse spatial cognitive impairment caused by Ribderived advanced glycation end products (AGEs) is correlated with the activation of an astrocytemediated, Receptor for AGEs (RAGE)-dependent inflammatory response
Rib is ingested as a supplement for cardiac energetic metabolism for instance the patients with stable coronary artery disease as the sugar provides the structural foundation for ATP.[26,27]
Summary
The roles of Rib in glycation and its resulting effects in vitro and in vivo have drawn increased attention in recent years.[3]. RAGE is an important signal transduction receptor activating an array of signal transduction cascades in response to AGE binding.[12] In present study, we report that Rib accelerated AGE formation both in U251 and U87MG astrocytoma cells and in mouse brain, and induced a corresponding upregulation of RAGE. Rib induced astrocyte activation in mouse hippocampus and impaired spatial learning and memory ability. These results suggest that mouse spatial cognitive impairment caused by Ribderived AGEs is correlated with the activation of an astrocytemediated, RAGE-dependent inflammatory response
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