Blocking TRAIL-DR5 signaling with soluble DR5 reduces delayed neuronal damage after transient global cerebral ischemia
Mechanisms underlying delayed selective neuronal death after global cerebral ischemia remain to be clarified. Here, we report a critical role for tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in the pathogenesis of cerebral ischemia. C57BL/6j mice were subjected to transient...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2010-08-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996110000902 |
| _version_ | 1819119471556558848 |
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| author | Min Cui Limei Wang Xiaohong Liang Xuelian Ma Yugang Liu Mingfeng Yang Kejing Liu Xinbing Wei Zhiqiang Zhou Youhai H. Chen Wensheng Sun |
| author_facet | Min Cui Limei Wang Xiaohong Liang Xuelian Ma Yugang Liu Mingfeng Yang Kejing Liu Xinbing Wei Zhiqiang Zhou Youhai H. Chen Wensheng Sun |
| author_sort | Min Cui |
| collection | DOAJ |
| description | Mechanisms underlying delayed selective neuronal death after global cerebral ischemia remain to be clarified. Here, we report a critical role for tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in the pathogenesis of cerebral ischemia. C57BL/6j mice were subjected to transient global brain ischemia. RT-PCR and immunohistochemistry showed that the expression of TRAIL and DR5 was upregulated following transient ischemia–reperfusion. Dual immunofluorescence analysis indicated that TRAIL expression was significantly more pronounced in astrocytes and activated microglia/macrophages, whereas DR5 expression was more pronounced in neurons, which had a good correlation with the distribution of apoptotic cells. Treatment with soluble DR5 reduced ischemic cell death after transient global ischemia through blocking the interaction of endogenous TRAIL with DR5. These results indicate that TRAIL plays a deleterious role in the pathogenesis of delayed neuronal damage after global cerebral ischemia and inhibition of TRAIL function in the brain may represent a novel neuroprotective strategy to treat ischemic stroke. |
| first_indexed | 2024-12-22T06:05:18Z |
| format | Article |
| id | doaj.art-faf62ae8407d45b4bd9ba38cb094b580 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-22T06:05:18Z |
| publishDate | 2010-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-faf62ae8407d45b4bd9ba38cb094b5802022-12-21T18:36:26ZengElsevierNeurobiology of Disease1095-953X2010-08-01392138147Blocking TRAIL-DR5 signaling with soluble DR5 reduces delayed neuronal damage after transient global cerebral ischemiaMin Cui0Limei Wang1Xiaohong Liang2Xuelian Ma3Yugang Liu4Mingfeng Yang5Kejing Liu6Xinbing Wei7Zhiqiang Zhou8Youhai H. Chen9Wensheng Sun10Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, P.R. China; Corresponding authors.School of Medicine and Pharmaceutics, Ocean University of China. Qingdao, Shandong, 266003, P.R. ChinaDepartment of Immunology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, P.R. ChinaDepartment of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, P.R. ChinaDepartment of Pathology and Pathophysiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, P.R. ChinaDepartment of Neurology; Affiliated Hospital of Taishan Medical College, Taian, Shandong, 271000, P.R. ChinaDepartment of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, P.R. ChinaDepartment of Pharmacology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, P.R. ChinaDepartment of Pathology and Pathophysiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, P.R. ChinaDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Immunology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, P.R. China; Corresponding authors.Mechanisms underlying delayed selective neuronal death after global cerebral ischemia remain to be clarified. Here, we report a critical role for tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in the pathogenesis of cerebral ischemia. C57BL/6j mice were subjected to transient global brain ischemia. RT-PCR and immunohistochemistry showed that the expression of TRAIL and DR5 was upregulated following transient ischemia–reperfusion. Dual immunofluorescence analysis indicated that TRAIL expression was significantly more pronounced in astrocytes and activated microglia/macrophages, whereas DR5 expression was more pronounced in neurons, which had a good correlation with the distribution of apoptotic cells. Treatment with soluble DR5 reduced ischemic cell death after transient global ischemia through blocking the interaction of endogenous TRAIL with DR5. These results indicate that TRAIL plays a deleterious role in the pathogenesis of delayed neuronal damage after global cerebral ischemia and inhibition of TRAIL function in the brain may represent a novel neuroprotective strategy to treat ischemic stroke.http://www.sciencedirect.com/science/article/pii/S0969996110000902TRAILDR5ApoptosisBrain ischemia |
| spellingShingle | Min Cui Limei Wang Xiaohong Liang Xuelian Ma Yugang Liu Mingfeng Yang Kejing Liu Xinbing Wei Zhiqiang Zhou Youhai H. Chen Wensheng Sun Blocking TRAIL-DR5 signaling with soluble DR5 reduces delayed neuronal damage after transient global cerebral ischemia Neurobiology of Disease TRAIL DR5 Apoptosis Brain ischemia |
| title | Blocking TRAIL-DR5 signaling with soluble DR5 reduces delayed neuronal damage after transient global cerebral ischemia |
| title_full | Blocking TRAIL-DR5 signaling with soluble DR5 reduces delayed neuronal damage after transient global cerebral ischemia |
| title_fullStr | Blocking TRAIL-DR5 signaling with soluble DR5 reduces delayed neuronal damage after transient global cerebral ischemia |
| title_full_unstemmed | Blocking TRAIL-DR5 signaling with soluble DR5 reduces delayed neuronal damage after transient global cerebral ischemia |
| title_short | Blocking TRAIL-DR5 signaling with soluble DR5 reduces delayed neuronal damage after transient global cerebral ischemia |
| title_sort | blocking trail dr5 signaling with soluble dr5 reduces delayed neuronal damage after transient global cerebral ischemia |
| topic | TRAIL DR5 Apoptosis Brain ischemia |
| url | http://www.sciencedirect.com/science/article/pii/S0969996110000902 |
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