l-lysine confers neuroprotection by suppressing inflammatory response via microRNA-575/PTEN signaling after mouse intracerebral hemorrhage injury
l-lysine is a basic amino acid that has been shown to exert neuroprotective effect. However, the underlying mechanism remains to be elucidated. In this study, we investigate how l-lysine exerts its neuroprotective effect in hemin-insulted mouse cortical neurons in vitro and the mouse model of intrac...
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creator | Cheng, Jing Tang, Jun-Chun Pan, Meng-Xian Chen, Song-Feng Zhao, Dan Zhang, Ya Liao, Hua-Bao Zhuang, Yang Lei, Rui-Xue Wang, Shu Liu, An-Chun Chen, Juan Zhang, Zhao-Hui Li, Huan-Ting Wan, Qi Chen, Qian-Xue |
description | l-lysine is a basic amino acid that has been shown to exert neuroprotective effect. However, the underlying mechanism remains to be elucidated. In this study, we investigate how l-lysine exerts its neuroprotective effect in hemin-insulted mouse cortical neurons in vitro and the mouse model of intracerebral hemorrhage (ICH) in vivo. We demonstrate that l-lysine treatment promotes M2 microglial polarization and reduces inflammatory response both in vitro and in vivo, suggesting that l-lysine may play a neuroprotective role in ICH injury. Indeed, we show that l-lysine treatment reduces cortical neuronal death after hemin insult in vitro and decrease the number of degenerating neurons after ICH in vivo. l-lysine also improves the functional recovery of ICH animals in neurobehavioral tests. Consistent with the role of PTEN in regulating inflammatory response, we find that PTEN inhibition promotes M2 microglial polarization and suppresses pro-inflammatory response in mouse ICH injury, which contribute to the neuroprotective effect of l-lysine. Moreover, our results reveal that microRNA-575 directly suppressed PTEN to promote M2 microglial polarization and mediate the neuroprotective effect of l-lysine in ICH injury. Together, our results suggest that l-lysine confers neuroprotection after ICH injury through enhancing M2 microglial polarization and reducing inflammatory response, which is mediated by microRNA-575 upregulation and subsequent PTEN downregulation.
•l-lysine confers neuroprotection after mouse intracerebral hemorrhage injury.•l-lysine promotes M2 microglial polarization and reduces inflammatory response.•l-lysine upregulates miRNA-575 and downregulates PTEN. |
doi_str_mv | 10.1016/j.expneurol.2020.113214 |
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•l-lysine confers neuroprotection after mouse intracerebral hemorrhage injury.•l-lysine promotes M2 microglial polarization and reduces inflammatory response.•l-lysine upregulates miRNA-575 and downregulates PTEN.</description><identifier>ISSN: 0014-4886</identifier><identifier>EISSN: 1090-2430</identifier><identifier>DOI: 10.1016/j.expneurol.2020.113214</identifier><identifier>PMID: 31987833</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Inflammatory response ; Intracerebral hemorrhage ; l-lysine ; M2 microglia ; MicroRNA-575 ; Neuroprotection ; PTEN</subject><ispartof>Experimental neurology, 2020-05, Vol.327 (C), p.113214-113214, Article 113214</ispartof><rights>2020 The Authors</rights><rights>Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c447t-f71d52c3586da9f77b3a27209f4ff28d4db6fe6db3daf7ada8f1703fe55df6ab3</citedby><cites>FETCH-LOGICAL-c447t-f71d52c3586da9f77b3a27209f4ff28d4db6fe6db3daf7ada8f1703fe55df6ab3</cites><orcidid>0000-0002-9413-1030 ; 0000000294131030</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.expneurol.2020.113214$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31987833$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/1596871$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Cheng, Jing</creatorcontrib><creatorcontrib>Tang, Jun-Chun</creatorcontrib><creatorcontrib>Pan, Meng-Xian</creatorcontrib><creatorcontrib>Chen, Song-Feng</creatorcontrib><creatorcontrib>Zhao, Dan</creatorcontrib><creatorcontrib>Zhang, Ya</creatorcontrib><creatorcontrib>Liao, Hua-Bao</creatorcontrib><creatorcontrib>Zhuang, Yang</creatorcontrib><creatorcontrib>Lei, Rui-Xue</creatorcontrib><creatorcontrib>Wang, Shu</creatorcontrib><creatorcontrib>Liu, An-Chun</creatorcontrib><creatorcontrib>Chen, Juan</creatorcontrib><creatorcontrib>Zhang, Zhao-Hui</creatorcontrib><creatorcontrib>Li, Huan-Ting</creatorcontrib><creatorcontrib>Wan, Qi</creatorcontrib><creatorcontrib>Chen, Qian-Xue</creatorcontrib><title>l-lysine confers neuroprotection by suppressing inflammatory response via microRNA-575/PTEN signaling after mouse intracerebral hemorrhage injury</title><title>Experimental neurology</title><addtitle>Exp Neurol</addtitle><description>l-lysine is a basic amino acid that has been shown to exert neuroprotective effect. However, the underlying mechanism remains to be elucidated. In this study, we investigate how l-lysine exerts its neuroprotective effect in hemin-insulted mouse cortical neurons in vitro and the mouse model of intracerebral hemorrhage (ICH) in vivo. We demonstrate that l-lysine treatment promotes M2 microglial polarization and reduces inflammatory response both in vitro and in vivo, suggesting that l-lysine may play a neuroprotective role in ICH injury. Indeed, we show that l-lysine treatment reduces cortical neuronal death after hemin insult in vitro and decrease the number of degenerating neurons after ICH in vivo. l-lysine also improves the functional recovery of ICH animals in neurobehavioral tests. Consistent with the role of PTEN in regulating inflammatory response, we find that PTEN inhibition promotes M2 microglial polarization and suppresses pro-inflammatory response in mouse ICH injury, which contribute to the neuroprotective effect of l-lysine. Moreover, our results reveal that microRNA-575 directly suppressed PTEN to promote M2 microglial polarization and mediate the neuroprotective effect of l-lysine in ICH injury. Together, our results suggest that l-lysine confers neuroprotection after ICH injury through enhancing M2 microglial polarization and reducing inflammatory response, which is mediated by microRNA-575 upregulation and subsequent PTEN downregulation.
•l-lysine confers neuroprotection after mouse intracerebral hemorrhage injury.•l-lysine promotes M2 microglial polarization and reduces inflammatory response.•l-lysine upregulates miRNA-575 and downregulates PTEN.</description><subject>Inflammatory response</subject><subject>Intracerebral hemorrhage</subject><subject>l-lysine</subject><subject>M2 microglia</subject><subject>MicroRNA-575</subject><subject>Neuroprotection</subject><subject>PTEN</subject><issn>0014-4886</issn><issn>1090-2430</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqFkctu1DAUhi0EokPhFcBixSZT3xIny1FVLlJVECpry4mPZzxK7GAnFXkM3hiHlG5ZWTr-zuX_f4TeUbKnhFZX5z38Gj3MMfR7RliuUs6oeIZ2lDSkYIKT52hHCBWFqOvqAr1K6UwIaQSTL9EFp00ta8536Hdf9EtyHnAXvIWY8N-pYwwTdJMLHrcLTvM4RkgZO2Lnba-HQU8hLjgXx-AT4Aen8eC6GL7fHYpSllff7m_ucHJHr_u1S9sJIh7CnFnnp6g7iNBG3eMTDCHGkz6uH-c5Lq_RC6v7BG8e30v04-PN_fXn4vbrpy_Xh9uiE0JOhZXUlKzjZV0Z3VgpW66ZZKSxwlpWG2HaykJlWm60ldro2lJJuIWyNLbSLb9E77e5IU1Opc5lwadsgs-6FS2bqpY0Qx82KBvyc4Y0qcGlDvpee8hiFONClqSuBcuo3NDsQkoRrBqjG3RcFCVqDU2d1VNoag1NbaHlzrePS-Z2APPU9y-lDBw2ALIfDw7iei74DoyL67UmuP8u-QOsKrFZ</recordid><startdate>202005</startdate><enddate>202005</enddate><creator>Cheng, Jing</creator><creator>Tang, Jun-Chun</creator><creator>Pan, Meng-Xian</creator><creator>Chen, Song-Feng</creator><creator>Zhao, Dan</creator><creator>Zhang, Ya</creator><creator>Liao, Hua-Bao</creator><creator>Zhuang, Yang</creator><creator>Lei, Rui-Xue</creator><creator>Wang, Shu</creator><creator>Liu, An-Chun</creator><creator>Chen, Juan</creator><creator>Zhang, Zhao-Hui</creator><creator>Li, Huan-Ting</creator><creator>Wan, Qi</creator><creator>Chen, Qian-Xue</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>OTOTI</scope><orcidid>https://orcid.org/0000-0002-9413-1030</orcidid><orcidid>https://orcid.org/0000000294131030</orcidid></search><sort><creationdate>202005</creationdate><title>l-lysine confers neuroprotection by suppressing inflammatory response via microRNA-575/PTEN signaling after mouse intracerebral hemorrhage injury</title><author>Cheng, Jing ; Tang, Jun-Chun ; Pan, Meng-Xian ; Chen, Song-Feng ; Zhao, Dan ; Zhang, Ya ; Liao, Hua-Bao ; Zhuang, Yang ; Lei, Rui-Xue ; Wang, Shu ; Liu, An-Chun ; Chen, Juan ; Zhang, Zhao-Hui ; Li, Huan-Ting ; Wan, Qi ; Chen, Qian-Xue</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c447t-f71d52c3586da9f77b3a27209f4ff28d4db6fe6db3daf7ada8f1703fe55df6ab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Inflammatory response</topic><topic>Intracerebral hemorrhage</topic><topic>l-lysine</topic><topic>M2 microglia</topic><topic>MicroRNA-575</topic><topic>Neuroprotection</topic><topic>PTEN</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cheng, Jing</creatorcontrib><creatorcontrib>Tang, Jun-Chun</creatorcontrib><creatorcontrib>Pan, Meng-Xian</creatorcontrib><creatorcontrib>Chen, Song-Feng</creatorcontrib><creatorcontrib>Zhao, Dan</creatorcontrib><creatorcontrib>Zhang, Ya</creatorcontrib><creatorcontrib>Liao, Hua-Bao</creatorcontrib><creatorcontrib>Zhuang, Yang</creatorcontrib><creatorcontrib>Lei, Rui-Xue</creatorcontrib><creatorcontrib>Wang, Shu</creatorcontrib><creatorcontrib>Liu, An-Chun</creatorcontrib><creatorcontrib>Chen, Juan</creatorcontrib><creatorcontrib>Zhang, Zhao-Hui</creatorcontrib><creatorcontrib>Li, Huan-Ting</creatorcontrib><creatorcontrib>Wan, Qi</creatorcontrib><creatorcontrib>Chen, Qian-Xue</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>Experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cheng, Jing</au><au>Tang, Jun-Chun</au><au>Pan, Meng-Xian</au><au>Chen, Song-Feng</au><au>Zhao, Dan</au><au>Zhang, Ya</au><au>Liao, Hua-Bao</au><au>Zhuang, Yang</au><au>Lei, Rui-Xue</au><au>Wang, Shu</au><au>Liu, An-Chun</au><au>Chen, Juan</au><au>Zhang, Zhao-Hui</au><au>Li, Huan-Ting</au><au>Wan, Qi</au><au>Chen, Qian-Xue</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>l-lysine confers neuroprotection by suppressing inflammatory response via microRNA-575/PTEN signaling after mouse intracerebral hemorrhage injury</atitle><jtitle>Experimental neurology</jtitle><addtitle>Exp Neurol</addtitle><date>2020-05</date><risdate>2020</risdate><volume>327</volume><issue>C</issue><spage>113214</spage><epage>113214</epage><pages>113214-113214</pages><artnum>113214</artnum><issn>0014-4886</issn><eissn>1090-2430</eissn><abstract>l-lysine is a basic amino acid that has been shown to exert neuroprotective effect. However, the underlying mechanism remains to be elucidated. In this study, we investigate how l-lysine exerts its neuroprotective effect in hemin-insulted mouse cortical neurons in vitro and the mouse model of intracerebral hemorrhage (ICH) in vivo. We demonstrate that l-lysine treatment promotes M2 microglial polarization and reduces inflammatory response both in vitro and in vivo, suggesting that l-lysine may play a neuroprotective role in ICH injury. Indeed, we show that l-lysine treatment reduces cortical neuronal death after hemin insult in vitro and decrease the number of degenerating neurons after ICH in vivo. l-lysine also improves the functional recovery of ICH animals in neurobehavioral tests. Consistent with the role of PTEN in regulating inflammatory response, we find that PTEN inhibition promotes M2 microglial polarization and suppresses pro-inflammatory response in mouse ICH injury, which contribute to the neuroprotective effect of l-lysine. Moreover, our results reveal that microRNA-575 directly suppressed PTEN to promote M2 microglial polarization and mediate the neuroprotective effect of l-lysine in ICH injury. Together, our results suggest that l-lysine confers neuroprotection after ICH injury through enhancing M2 microglial polarization and reducing inflammatory response, which is mediated by microRNA-575 upregulation and subsequent PTEN downregulation.
•l-lysine confers neuroprotection after mouse intracerebral hemorrhage injury.•l-lysine promotes M2 microglial polarization and reduces inflammatory response.•l-lysine upregulates miRNA-575 and downregulates PTEN.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>31987833</pmid><doi>10.1016/j.expneurol.2020.113214</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-9413-1030</orcidid><orcidid>https://orcid.org/0000000294131030</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Inflammatory response Intracerebral hemorrhage l-lysine M2 microglia MicroRNA-575 Neuroprotection PTEN |
title | l-lysine confers neuroprotection by suppressing inflammatory response via microRNA-575/PTEN signaling after mouse intracerebral hemorrhage injury |
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