Effects of ginkgo biloba extract EGb761 on expression of RAGE and LRP-1 in cerebral microvascular endothelial cells under chronic hypoxia and hypoglycemia |
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Authors: | Fu-Ling Yan Ying Zheng Feng-Di Zhao |
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Institution: | (1) Department of Neurology, Zhongda Hospital, Southeast University, 210009 Nanjing, China;(2) Department of Physiology and Pathophysiology, Fudan University, Shanghai, China |
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Abstract: | Alzheimer’s disease (AD), characterized by accumulation of amyloid-beta protein (Aβ) in brain parenchyma, is closely associated
with brain ischemia. Decreased clearance of Aβ from brain is the main cause of Aβ accumulation in sporadic AD. However, the
mechanisms underlying ischemia-mediated AD pathogenesis remain unclear. The receptor for advanced end glycation products (RAGE)
and low-density lipoprotein receptor-related protein-1 (LRP-1) expressed at blood brain barrier (BBB) are actively involved
in Aβ clearance. RAGE is thought to be a primary transporter of Aβ across BBB into the brain from the systemic circulation,
while LRP-1 mediates the transport of Aβ out of the brain. Ginkgo biloba extract EGb761, a traditional Chinese medicine, has
been widely used in the treatment of AD. To investigate the effects of EGb761 on the expression of RAGE and LRP-1 in endothelial
cells in response to ischemic injury, we cultured bEnd.3 cells, an immortalized mouse cerebral microvessel endothelial cell
line, under a chronic hypoxic and hypoglycemic condition (CHH) to mimic ischemic injury of BBB, and then treated with EGb
761. We found that EGb 761 markedly ameliorated the damage (evaluated by MTT assay) from CHH. Moreover, we demonstrated that
CHH led to a significant increase in the expression of RAGE both at the mRNA and protein levels at all times (24, 36, and
48 h), conversely; CHH induced a dramatic decrease in LRP-1 mRNA and protein expression at both 36 and 48 h. The results indicated
that CHH has differential effects on the expression of RAGE and LRP-1. Furthermore, EGb761 significantly reversed CHH-induced
upregulation of RAGE expression and downregulation of LRP-1 expression. Our findings suggest that EGb761 favor clearance of
Aβ via regulating the expression of RAGE and LRP-1 during brain ischemia. This may provide a new insight into a possible molecular
mechanism underlying brain ischemia-mediated AD pathogenesis, and potential therapeutic application of EGb 761 in treatment
of AD. |
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Keywords: | Hypoxia hypoglycemia Cerebral microvascular endothelial cells LRP-1 RAGE EGb 761 |
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