Neuroprotective Effects of Endogenous Secretory Receptor for Advanced Glycation End-products in Brain Ischemia
| Autor: | Ai Harashima, Masahiro Oishi, Yasuhiko Hayashi, Mitsutoshi Nakada, Yasuko Kitao, Nontaphat Leerach, Seiichi Munesue, Osamu Hori, Yasuhiko Yamamoto, Yu Shimizu, Hiroshi Yamamoto, Tsuyoshi Hattori |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Programmed cell death medicine.medical_specialty Ischemia Blood–brain barrier Neuroprotection Orginal Article Pathology and Forensic Medicine RAGE (receptor) Brain ischemia 03 medical and health sciences 0302 clinical medicine Glycation Receptor for advanced glycation end-products (RAGE) Internal medicine medicine cardiovascular diseases Receptor Chemistry delayed neuronal cell damage Cell Biology blood-brain barrier medicine.disease 030104 developmental biology medicine.anatomical_structure Endocrinology cardiovascular system Neurology (clinical) parabiosis Geriatrics and Gerontology endogenous secretory RAGE (esRAGE) 030217 neurology & neurosurgery |
| Zdroj: | Aging and Disease |
| ISSN: | 2152-5250 |
| Popis: | The receptor for advanced glycation end-products (RAGE) is expressed on human brain endothelial cells (HBEC) and is implicated in neuronal cell death after ischemia. We report that endogenous secretory RAGE (esRAGE) is a splicing variant form of RAGE that functions as a decoy against ischemia-induced neuronal cell damage. This study demonstrated that esRAGE was associated with heparan sulphate proteoglycans on HBEC. The parabiotic experiments between human esRAGE overexpressing transgenic (Tg), RAGE knockout (KO), and wild-type (WT) mice revealed a significant neuronal cell damage in the CA1 region of the WT side of parabiotic WT→WT mice, but not of Tg→WT mice, 7 days after bilateral common carotid artery occlusion. Human esRAGE was detected around the CA1 neurons in the WT side of the parabiotic Tg→WT pair, but not in the KO side of the Tg→KO pair. To elucidate the dynamic transfer of esRAGE into the brain, we used the blood-brain barrier (BBB) system (PharmaCo-Cell) with or without RAGE knockdown in endothelial cells. A RAGE-dependent transfer of esRAGE was demonstrated from the vascular to the brain side. These findings suggested that esRAGE is associated with heparan sulphate proteoglycans and is transferred into the brain via BBB to exert its neuroprotective effects in ischemia. |
| Databáze: | OpenAIRE |
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