Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice
Cathepsin S (CatS) is a cysteine protease normally present in lysosomes. It has long been regarded as an enzyme that is primarily involved in general protein degradation. More recently, mounting evidence has shown that it is involved in Alzheimer disease, seizures, age-related inflammatory processes...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/187873 |
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| _version_ | 1832566726257016832 |
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| author | Jianguo Xu Handong Wang Ke Ding Xinyu Lu Tao Li Jiawei Wang Chunxi Wang Jian Wang |
| author_facet | Jianguo Xu Handong Wang Ke Ding Xinyu Lu Tao Li Jiawei Wang Chunxi Wang Jian Wang |
| author_sort | Jianguo Xu |
| collection | DOAJ |
| description | Cathepsin S (CatS) is a cysteine protease normally present in lysosomes. It has long been regarded as an enzyme that is primarily involved in general protein degradation. More recently, mounting evidence has shown that it is involved in Alzheimer disease, seizures, age-related inflammatory processes, and neuropathic pain. In this study, we investigated the time course of CatS protein and mRNA expression and the cellular distribution of CatS in a mouse model of traumatic brain injury (TBI). To clarify the roles of CatS in TBI, we injected the mice intraventricularly with LHVS, a nonbrain penetrant, irreversible CatS inhibitor, and examined the effect on inflammation and neurobehavioral function. We found that expression of CatS was increased as early as 1 h after TBI at both protein and mRNA levels. The increased expression was detected in microglia and neurons. Inhibition of CatS significantly reduced the level of TBI-induced inflammatory factors in brain tissue and alleviated brain edema. Additionally, administration of LHVS led to a decrease in neuronal degeneration and improved neurobehavioral function. These results imply that CatS is involved in the secondary injury after TBI and provide a new perspective for preventing secondary injury after TBI. |
| format | Article |
| id | doaj-art-f4dfb3f87a2947ab9d448a358bc7f342 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-f4dfb3f87a2947ab9d448a358bc7f3422025-02-03T01:03:23ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/187873187873Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in MiceJianguo Xu0Handong Wang1Ke Ding2Xinyu Lu3Tao Li4Jiawei Wang5Chunxi Wang6Jian Wang7Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, ChinaDepartment of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, ChinaDepartment of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, ChinaDepartment of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, ChinaDepartment of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, ChinaDepartment of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, ChinaDepartment of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, ChinaDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21218, USACathepsin S (CatS) is a cysteine protease normally present in lysosomes. It has long been regarded as an enzyme that is primarily involved in general protein degradation. More recently, mounting evidence has shown that it is involved in Alzheimer disease, seizures, age-related inflammatory processes, and neuropathic pain. In this study, we investigated the time course of CatS protein and mRNA expression and the cellular distribution of CatS in a mouse model of traumatic brain injury (TBI). To clarify the roles of CatS in TBI, we injected the mice intraventricularly with LHVS, a nonbrain penetrant, irreversible CatS inhibitor, and examined the effect on inflammation and neurobehavioral function. We found that expression of CatS was increased as early as 1 h after TBI at both protein and mRNA levels. The increased expression was detected in microglia and neurons. Inhibition of CatS significantly reduced the level of TBI-induced inflammatory factors in brain tissue and alleviated brain edema. Additionally, administration of LHVS led to a decrease in neuronal degeneration and improved neurobehavioral function. These results imply that CatS is involved in the secondary injury after TBI and provide a new perspective for preventing secondary injury after TBI.http://dx.doi.org/10.1155/2013/187873 |
| spellingShingle | Jianguo Xu Handong Wang Ke Ding Xinyu Lu Tao Li Jiawei Wang Chunxi Wang Jian Wang Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice Mediators of Inflammation |
| title | Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice |
| title_full | Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice |
| title_fullStr | Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice |
| title_full_unstemmed | Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice |
| title_short | Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice |
| title_sort | inhibition of cathepsin s produces neuroprotective effects after traumatic brain injury in mice |
| url | http://dx.doi.org/10.1155/2013/187873 |
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