Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Xu, Jianguo, Wang, Handong, Ding, Ke, Lu, Xinyu, Li, Tao, Wang, Jiawei, Wang, Chunxi, Wang, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824312/
https://www.ncbi.nlm.nih.gov/pubmed/24282339
http://dx.doi.org/10.1155/2013/187873
_version_ 1782290690966814720
author Xu, Jianguo
Wang, Handong
Ding, Ke
Lu, Xinyu
Li, Tao
Wang, Jiawei
Wang, Chunxi
Wang, Jian
author_facet Xu, Jianguo
Wang, Handong
Ding, Ke
Lu, Xinyu
Li, Tao
Wang, Jiawei
Wang, Chunxi
Wang, Jian
author_sort Xu, Jianguo
collection PubMed
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 Online
Article
Text
id pubmed-3824312
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Hindawi Publishing Corporation
record_format MEDLINE/PubMed
spelling pubmed-38243122013-11-26 Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice Xu, Jianguo Wang, Handong Ding, Ke Lu, Xinyu Li, Tao Wang, Jiawei Wang, Chunxi Wang, Jian Mediators Inflamm Research Article 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. Hindawi Publishing Corporation 2013 2013-10-24 /pmc/articles/PMC3824312/ /pubmed/24282339 http://dx.doi.org/10.1155/2013/187873 Text en Copyright © 2013 Jianguo Xu et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Xu, Jianguo
Wang, Handong
Ding, Ke
Lu, Xinyu
Li, Tao
Wang, Jiawei
Wang, Chunxi
Wang, Jian
Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824312/
https://www.ncbi.nlm.nih.gov/pubmed/24282339
http://dx.doi.org/10.1155/2013/187873
work_keys_str_mv AT xujianguo inhibitionofcathepsinsproducesneuroprotectiveeffectsaftertraumaticbraininjuryinmice
AT wanghandong inhibitionofcathepsinsproducesneuroprotectiveeffectsaftertraumaticbraininjuryinmice
AT dingke inhibitionofcathepsinsproducesneuroprotectiveeffectsaftertraumaticbraininjuryinmice
AT luxinyu inhibitionofcathepsinsproducesneuroprotectiveeffectsaftertraumaticbraininjuryinmice
AT litao inhibitionofcathepsinsproducesneuroprotectiveeffectsaftertraumaticbraininjuryinmice
AT wangjiawei inhibitionofcathepsinsproducesneuroprotectiveeffectsaftertraumaticbraininjuryinmice
AT wangchunxi inhibitionofcathepsinsproducesneuroprotectiveeffectsaftertraumaticbraininjuryinmice
AT wangjian inhibitionofcathepsinsproducesneuroprotectiveeffectsaftertraumaticbraininjuryinmice