ASK1 phosphorylation regulates astrocytic reactive gliosis in vitro and in vivo
•Both ASK1 and the downstream signal P38 are activated in trauma-induced reactive gliosis in vitro and in vivo.•The phosphorylation of ASK1 is accompanied by dissociation of 14-3-3 during astrocyte activation after injury.•Trx reduces trauma-induced reactive gliosis through inhibition of ASK1 phosph...
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Veröffentlicht in: | Neuroscience letters 2020-01, Vol.716, p.134675-134675, Article 134675 |
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creator | Li, Tianzun Xu, Rui Xia, Haijian Hu, Xiaojun Wang, Shengxi Li, Yang Yan, Yi Xia, Yongzhi |
description | •Both ASK1 and the downstream signal P38 are activated in trauma-induced reactive gliosis in vitro and in vivo.•The phosphorylation of ASK1 is accompanied by dissociation of 14-3-3 during astrocyte activation after injury.•Trx reduces trauma-induced reactive gliosis through inhibition of ASK1 phosphorylation.
Apoptosis signal-regulating kinase 1 (ASK1) may play a pivotal role in reactive gliosis. To assess the role of ASK1 in trauma-induced reactive gliosis, we examined the phosphorylation of ASK1 and the expression of glial fibrillary acidic protein (GFAP) and vimentin after scratch injury in cultured astrocytes and spinal cord injury (SCI) in rats. Enhanced phosphorylation of ASK1 was detected during reactive gliosis both in vitro and in vivo, and P38 MAPK relayed the signal from phosphorylated ASK1 to the activation of astrocytes. Immunoprecipitation analyses suggested that 14-3-3 was dissociated from ASK1 during astrocyte activation. Finally, treatment with thioredoxin reduced ASK1 phosphorylation and reactive gliosis and promoted hindlimb locomotion recovery in SCI rats. These results indicated that ASK1 may play an important role in mechanical-injury-induced reactive gliosis. |
doi_str_mv | 10.1016/j.neulet.2019.134675 |
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Apoptosis signal-regulating kinase 1 (ASK1) may play a pivotal role in reactive gliosis. To assess the role of ASK1 in trauma-induced reactive gliosis, we examined the phosphorylation of ASK1 and the expression of glial fibrillary acidic protein (GFAP) and vimentin after scratch injury in cultured astrocytes and spinal cord injury (SCI) in rats. Enhanced phosphorylation of ASK1 was detected during reactive gliosis both in vitro and in vivo, and P38 MAPK relayed the signal from phosphorylated ASK1 to the activation of astrocytes. Immunoprecipitation analyses suggested that 14-3-3 was dissociated from ASK1 during astrocyte activation. Finally, treatment with thioredoxin reduced ASK1 phosphorylation and reactive gliosis and promoted hindlimb locomotion recovery in SCI rats. These results indicated that ASK1 may play an important role in mechanical-injury-induced reactive gliosis.</description><identifier>ISSN: 0304-3940</identifier><identifier>EISSN: 1872-7972</identifier><identifier>DOI: 10.1016/j.neulet.2019.134675</identifier><identifier>PMID: 31830507</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Animals ; Apoptosis signal-regulating kinase 1 ; Astrocyte ; Astrocytes - metabolism ; Astrocytes - pathology ; Female ; Glial fibrillary acidic protein ; Gliosis - metabolism ; Gliosis - pathology ; MAP Kinase Kinase Kinase 5 - metabolism ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Reactive gliosis ; Spinal Cord Injuries - metabolism ; Spinal Cord Injuries - pathology ; Spinal cord injury ; Thioredoxin</subject><ispartof>Neuroscience letters, 2020-01, Vol.716, p.134675-134675, Article 134675</ispartof><rights>2019 Elsevier B.V.</rights><rights>Copyright © 2019 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-cc3372ddfc0139a938b5f29b5656c695d472d4c0537fcd66e685a7a31b5423093</citedby><cites>FETCH-LOGICAL-c428t-cc3372ddfc0139a938b5f29b5656c695d472d4c0537fcd66e685a7a31b5423093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neulet.2019.134675$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31830507$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Tianzun</creatorcontrib><creatorcontrib>Xu, Rui</creatorcontrib><creatorcontrib>Xia, Haijian</creatorcontrib><creatorcontrib>Hu, Xiaojun</creatorcontrib><creatorcontrib>Wang, Shengxi</creatorcontrib><creatorcontrib>Li, Yang</creatorcontrib><creatorcontrib>Yan, Yi</creatorcontrib><creatorcontrib>Xia, Yongzhi</creatorcontrib><title>ASK1 phosphorylation regulates astrocytic reactive gliosis in vitro and in vivo</title><title>Neuroscience letters</title><addtitle>Neurosci Lett</addtitle><description>•Both ASK1 and the downstream signal P38 are activated in trauma-induced reactive gliosis in vitro and in vivo.•The phosphorylation of ASK1 is accompanied by dissociation of 14-3-3 during astrocyte activation after injury.•Trx reduces trauma-induced reactive gliosis through inhibition of ASK1 phosphorylation.
Apoptosis signal-regulating kinase 1 (ASK1) may play a pivotal role in reactive gliosis. To assess the role of ASK1 in trauma-induced reactive gliosis, we examined the phosphorylation of ASK1 and the expression of glial fibrillary acidic protein (GFAP) and vimentin after scratch injury in cultured astrocytes and spinal cord injury (SCI) in rats. Enhanced phosphorylation of ASK1 was detected during reactive gliosis both in vitro and in vivo, and P38 MAPK relayed the signal from phosphorylated ASK1 to the activation of astrocytes. Immunoprecipitation analyses suggested that 14-3-3 was dissociated from ASK1 during astrocyte activation. Finally, treatment with thioredoxin reduced ASK1 phosphorylation and reactive gliosis and promoted hindlimb locomotion recovery in SCI rats. These results indicated that ASK1 may play an important role in mechanical-injury-induced reactive gliosis.</description><subject>Animals</subject><subject>Apoptosis signal-regulating kinase 1</subject><subject>Astrocyte</subject><subject>Astrocytes - metabolism</subject><subject>Astrocytes - pathology</subject><subject>Female</subject><subject>Glial fibrillary acidic protein</subject><subject>Gliosis - metabolism</subject><subject>Gliosis - pathology</subject><subject>MAP Kinase Kinase Kinase 5 - metabolism</subject><subject>Phosphorylation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reactive gliosis</subject><subject>Spinal Cord Injuries - metabolism</subject><subject>Spinal Cord Injuries - pathology</subject><subject>Spinal cord injury</subject><subject>Thioredoxin</subject><issn>0304-3940</issn><issn>1872-7972</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLAzEQx4Motla_gcgevWzNc7O5CEV8YaEH9RzS7GxN2W5qslvotzdlq0cPw7z-M8P8ELomeEowKe7W0xb6BropxURNCeOFFCdoTEpJc6kkPUVjzDDPmeJ4hC5iXGOMBRH8HI0YKRkWWI7RYvb-RrLtl4_Jwr4xnfNtFmDVpxBiZmIXvN13zqaisZ3bQbZqnI8uZq7Ndi61M9NWQ7Lzl-isNk2Eq6OfoM-nx4-Hl3y-eH59mM1zy2nZ5dYyJmlV1RYTpoxi5VLUVC1FIQpbKFHx1OUWCyZrWxUFFKUw0jCyFJwyrNgE3Q57t8F_9xA7vXHRQtOYFnwfNWW0ZFxhJZOUD1IbfIwBar0NbmPCXhOsDyj1Wg8o9QGlHlCmsZvjhX65gepv6JddEtwPAkh_7hwEHa2D1kLlAthOV979f-EH49eGqw</recordid><startdate>20200118</startdate><enddate>20200118</enddate><creator>Li, Tianzun</creator><creator>Xu, Rui</creator><creator>Xia, Haijian</creator><creator>Hu, Xiaojun</creator><creator>Wang, Shengxi</creator><creator>Li, Yang</creator><creator>Yan, Yi</creator><creator>Xia, Yongzhi</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20200118</creationdate><title>ASK1 phosphorylation regulates astrocytic reactive gliosis in vitro and in vivo</title><author>Li, Tianzun ; Xu, Rui ; Xia, Haijian ; Hu, Xiaojun ; Wang, Shengxi ; Li, Yang ; Yan, Yi ; Xia, Yongzhi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-cc3372ddfc0139a938b5f29b5656c695d472d4c0537fcd66e685a7a31b5423093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Apoptosis signal-regulating kinase 1</topic><topic>Astrocyte</topic><topic>Astrocytes - metabolism</topic><topic>Astrocytes - pathology</topic><topic>Female</topic><topic>Glial fibrillary acidic protein</topic><topic>Gliosis - metabolism</topic><topic>Gliosis - pathology</topic><topic>MAP Kinase Kinase Kinase 5 - metabolism</topic><topic>Phosphorylation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reactive gliosis</topic><topic>Spinal Cord Injuries - metabolism</topic><topic>Spinal Cord Injuries - pathology</topic><topic>Spinal cord injury</topic><topic>Thioredoxin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Tianzun</creatorcontrib><creatorcontrib>Xu, Rui</creatorcontrib><creatorcontrib>Xia, Haijian</creatorcontrib><creatorcontrib>Hu, Xiaojun</creatorcontrib><creatorcontrib>Wang, Shengxi</creatorcontrib><creatorcontrib>Li, Yang</creatorcontrib><creatorcontrib>Yan, Yi</creatorcontrib><creatorcontrib>Xia, Yongzhi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Neuroscience letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Tianzun</au><au>Xu, Rui</au><au>Xia, Haijian</au><au>Hu, Xiaojun</au><au>Wang, Shengxi</au><au>Li, Yang</au><au>Yan, Yi</au><au>Xia, Yongzhi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ASK1 phosphorylation regulates astrocytic reactive gliosis in vitro and in vivo</atitle><jtitle>Neuroscience letters</jtitle><addtitle>Neurosci Lett</addtitle><date>2020-01-18</date><risdate>2020</risdate><volume>716</volume><spage>134675</spage><epage>134675</epage><pages>134675-134675</pages><artnum>134675</artnum><issn>0304-3940</issn><eissn>1872-7972</eissn><abstract>•Both ASK1 and the downstream signal P38 are activated in trauma-induced reactive gliosis in vitro and in vivo.•The phosphorylation of ASK1 is accompanied by dissociation of 14-3-3 during astrocyte activation after injury.•Trx reduces trauma-induced reactive gliosis through inhibition of ASK1 phosphorylation.
Apoptosis signal-regulating kinase 1 (ASK1) may play a pivotal role in reactive gliosis. To assess the role of ASK1 in trauma-induced reactive gliosis, we examined the phosphorylation of ASK1 and the expression of glial fibrillary acidic protein (GFAP) and vimentin after scratch injury in cultured astrocytes and spinal cord injury (SCI) in rats. Enhanced phosphorylation of ASK1 was detected during reactive gliosis both in vitro and in vivo, and P38 MAPK relayed the signal from phosphorylated ASK1 to the activation of astrocytes. Immunoprecipitation analyses suggested that 14-3-3 was dissociated from ASK1 during astrocyte activation. Finally, treatment with thioredoxin reduced ASK1 phosphorylation and reactive gliosis and promoted hindlimb locomotion recovery in SCI rats. These results indicated that ASK1 may play an important role in mechanical-injury-induced reactive gliosis.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>31830507</pmid><doi>10.1016/j.neulet.2019.134675</doi><tpages>1</tpages></addata></record> |
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subjects | Animals Apoptosis signal-regulating kinase 1 Astrocyte Astrocytes - metabolism Astrocytes - pathology Female Glial fibrillary acidic protein Gliosis - metabolism Gliosis - pathology MAP Kinase Kinase Kinase 5 - metabolism Phosphorylation Rats Rats, Sprague-Dawley Reactive gliosis Spinal Cord Injuries - metabolism Spinal Cord Injuries - pathology Spinal cord injury Thioredoxin |
title | ASK1 phosphorylation regulates astrocytic reactive gliosis in vitro and in vivo |
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