Carnosol as a Nrf2 Activator Improves Endothelial Barrier Function Through Antioxidative Mechanisms
Oxidative stress is the main pathogenesis of diabetic microangiopathy, which can cause microvascular endothelial cell damage and destroy vascular barrier. In this study, it is found that carnosol protects human microvascular endothelial cells (HMVEC) through antioxidative mechanisms. First, we measu...
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| Veröffentlicht in: | International journal of molecular sciences 2019-02, Vol.20 (4), p.880 |
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| creator | Li, Xi Zhang, Qiao Hou, Ning Li, Jing Liu, Min Peng, Sha Zhang, Yuxin Luo, Yinzhen Zhao, Bowen Wang, Shifeng Zhang, Yanling Qiao, Yanjiang |
| description | Oxidative stress is the main pathogenesis of diabetic microangiopathy, which can cause microvascular endothelial cell damage and destroy vascular barrier. In this study, it is found that carnosol protects human microvascular endothelial cells (HMVEC) through antioxidative mechanisms. First, we measured the antioxidant activity of carnosol. We showed that carnosol pretreatment suppressed tert-butyl hydroperoxide (t-BHP)-induced cell viability, affected the production of lactate dehydrogenase (LDH) as well as reactive oxygen species (ROS), and increased the produce of nitric oxide (NO). Additionally, carnosol promotes the protein expression of vascular endothelial cadherin (VE-cadherin) to keep the integrity of intercellular junctions, which indicated that it protected microvascular barrier in oxidative stress. Meanwhile, we investigated that carnosol can interrupt Nrf2-Keap1 protein-protein interaction and stimulated antioxidant-responsive element (ARE)-driven luciferase activity in vitro. Mechanistically, we showed that carnosol promotes the expression of heme oxygenase 1(HO-1) and nuclear factor-erythroid 2 related factor 2(Nrf2). It can also promote the expression of endothelial nitric oxide synthase (eNOS). Collectively, our data support the notion that carnosol is a protective agent in HMVECs and has the potential for therapeutic use in the treatments of microvascular endothelial cell injury. |
| doi_str_mv | 10.3390/ijms20040880 |
| format | Article |
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In this study, it is found that carnosol protects human microvascular endothelial cells (HMVEC) through antioxidative mechanisms. First, we measured the antioxidant activity of carnosol. We showed that carnosol pretreatment suppressed tert-butyl hydroperoxide (t-BHP)-induced cell viability, affected the production of lactate dehydrogenase (LDH) as well as reactive oxygen species (ROS), and increased the produce of nitric oxide (NO). Additionally, carnosol promotes the protein expression of vascular endothelial cadherin (VE-cadherin) to keep the integrity of intercellular junctions, which indicated that it protected microvascular barrier in oxidative stress. Meanwhile, we investigated that carnosol can interrupt Nrf2-Keap1 protein-protein interaction and stimulated antioxidant-responsive element (ARE)-driven luciferase activity in vitro. Mechanistically, we showed that carnosol promotes the expression of heme oxygenase 1(HO-1) and nuclear factor-erythroid 2 related factor 2(Nrf2). It can also promote the expression of endothelial nitric oxide synthase (eNOS). Collectively, our data support the notion that carnosol is a protective agent in HMVECs and has the potential for therapeutic use in the treatments of microvascular endothelial cell injury.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms20040880</identifier><identifier>PMID: 30781644</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antigens, CD - metabolism ; Antioxidants ; Antioxidants - pharmacology ; Apoptosis ; Benzothiazoles - metabolism ; Cadherins - metabolism ; Cell injury ; Cell Line ; Cell membranes ; Cytoprotection - drug effects ; Cytoprotection - genetics ; Cytotoxicity ; Diabetes ; Diabetes mellitus ; Diabetic neuropathy ; Diabetic retinopathy ; Diterpenes, Abietane - chemistry ; Diterpenes, Abietane - pharmacology ; Endothelial Cells - drug effects ; Endothelial Cells - metabolism ; Endothelium ; Free Radical Scavengers - metabolism ; Humans ; Hyperglycemia ; Intracellular ; Localization ; Lysis ; Microvessels - pathology ; Molecular Docking Simulation ; NF-E2-Related Factor 2 - metabolism ; Nitric Oxide - metabolism ; Oxidative stress ; Proteins ; Reactive Oxygen Species - metabolism ; Sulfonic Acids - metabolism ; tert-Butylhydroperoxide</subject><ispartof>International journal of molecular sciences, 2019-02, Vol.20 (4), p.880</ispartof><rights>2019. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-99e265cc12732a5a35dba2b49eac1f21cff7d0c62466b062cc671f8fd78bb3e53</citedby><cites>FETCH-LOGICAL-c412t-99e265cc12732a5a35dba2b49eac1f21cff7d0c62466b062cc671f8fd78bb3e53</cites><orcidid>0000-0002-4999-8436</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413211/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413211/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30781644$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Xi</creatorcontrib><creatorcontrib>Zhang, Qiao</creatorcontrib><creatorcontrib>Hou, Ning</creatorcontrib><creatorcontrib>Li, Jing</creatorcontrib><creatorcontrib>Liu, Min</creatorcontrib><creatorcontrib>Peng, Sha</creatorcontrib><creatorcontrib>Zhang, Yuxin</creatorcontrib><creatorcontrib>Luo, Yinzhen</creatorcontrib><creatorcontrib>Zhao, Bowen</creatorcontrib><creatorcontrib>Wang, Shifeng</creatorcontrib><creatorcontrib>Zhang, Yanling</creatorcontrib><creatorcontrib>Qiao, Yanjiang</creatorcontrib><title>Carnosol as a Nrf2 Activator Improves Endothelial Barrier Function Through Antioxidative Mechanisms</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Oxidative stress is the main pathogenesis of diabetic microangiopathy, which can cause microvascular endothelial cell damage and destroy vascular barrier. In this study, it is found that carnosol protects human microvascular endothelial cells (HMVEC) through antioxidative mechanisms. First, we measured the antioxidant activity of carnosol. We showed that carnosol pretreatment suppressed tert-butyl hydroperoxide (t-BHP)-induced cell viability, affected the production of lactate dehydrogenase (LDH) as well as reactive oxygen species (ROS), and increased the produce of nitric oxide (NO). Additionally, carnosol promotes the protein expression of vascular endothelial cadherin (VE-cadherin) to keep the integrity of intercellular junctions, which indicated that it protected microvascular barrier in oxidative stress. Meanwhile, we investigated that carnosol can interrupt Nrf2-Keap1 protein-protein interaction and stimulated antioxidant-responsive element (ARE)-driven luciferase activity in vitro. Mechanistically, we showed that carnosol promotes the expression of heme oxygenase 1(HO-1) and nuclear factor-erythroid 2 related factor 2(Nrf2). It can also promote the expression of endothelial nitric oxide synthase (eNOS). Collectively, our data support the notion that carnosol is a protective agent in HMVECs and has the potential for therapeutic use in the treatments of microvascular endothelial cell injury.</description><subject>Antigens, CD - metabolism</subject><subject>Antioxidants</subject><subject>Antioxidants - pharmacology</subject><subject>Apoptosis</subject><subject>Benzothiazoles - metabolism</subject><subject>Cadherins - metabolism</subject><subject>Cell injury</subject><subject>Cell Line</subject><subject>Cell membranes</subject><subject>Cytoprotection - drug effects</subject><subject>Cytoprotection - genetics</subject><subject>Cytotoxicity</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetic neuropathy</subject><subject>Diabetic retinopathy</subject><subject>Diterpenes, Abietane - chemistry</subject><subject>Diterpenes, Abietane - pharmacology</subject><subject>Endothelial Cells - drug effects</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelium</subject><subject>Free Radical Scavengers - metabolism</subject><subject>Humans</subject><subject>Hyperglycemia</subject><subject>Intracellular</subject><subject>Localization</subject><subject>Lysis</subject><subject>Microvessels - pathology</subject><subject>Molecular Docking Simulation</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Nitric Oxide - metabolism</subject><subject>Oxidative stress</subject><subject>Proteins</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Sulfonic Acids - metabolism</subject><subject>tert-Butylhydroperoxide</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkUFv1DAQhS0EoqVw44wsceHAwnjsOMkFabtqaaUCl3K2Jo7TeJXYi52s6L9vqpZqy2lmNN88zdNj7L2AL1LW8NVvx4wACqoKXrBjoRBXALp8edAfsTc5bwFQYlG_ZkcSykpopY6Z3VAKMceBU-bEf6YO-dpOfk9TTPxy3KW4d5mfhTZOvRs8DfyUUvIu8fM5LGAM_LpPcb7p-Tos41_f0nLu-A9newo-j_kte9XRkN27x3rCfp-fXW8uVle_vl9u1lcrqwROq7p2qAtrBZYSqSBZtA1ho2pHVnQobNeVLViNSusGNFqrS9FVXVtWTSNdIU_Ytwfd3dyMrrUuTIkGs0t-pHRrInnzfBN8b27i3mglJAqxCHx6FEjxz-zyZEafrRsGCi7O2aColFAA9T368T90G-cUFnsGpURQqOtyoT4_UDbFnJPrnp4RYO7TM4fpLfiHQwNP8L-45B0yeZdc</recordid><startdate>20190218</startdate><enddate>20190218</enddate><creator>Li, Xi</creator><creator>Zhang, Qiao</creator><creator>Hou, Ning</creator><creator>Li, Jing</creator><creator>Liu, Min</creator><creator>Peng, Sha</creator><creator>Zhang, Yuxin</creator><creator>Luo, Yinzhen</creator><creator>Zhao, Bowen</creator><creator>Wang, Shifeng</creator><creator>Zhang, Yanling</creator><creator>Qiao, Yanjiang</creator><general>MDPI AG</general><general>MDPI</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4999-8436</orcidid></search><sort><creationdate>20190218</creationdate><title>Carnosol as a Nrf2 Activator Improves Endothelial Barrier Function Through Antioxidative Mechanisms</title><author>Li, Xi ; Zhang, Qiao ; Hou, Ning ; Li, Jing ; Liu, Min ; Peng, Sha ; Zhang, Yuxin ; Luo, Yinzhen ; Zhao, Bowen ; Wang, Shifeng ; Zhang, Yanling ; Qiao, Yanjiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-99e265cc12732a5a35dba2b49eac1f21cff7d0c62466b062cc671f8fd78bb3e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Antigens, CD - metabolism</topic><topic>Antioxidants</topic><topic>Antioxidants - pharmacology</topic><topic>Apoptosis</topic><topic>Benzothiazoles - metabolism</topic><topic>Cadherins - metabolism</topic><topic>Cell injury</topic><topic>Cell Line</topic><topic>Cell membranes</topic><topic>Cytoprotection - drug effects</topic><topic>Cytoprotection - genetics</topic><topic>Cytotoxicity</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetic neuropathy</topic><topic>Diabetic retinopathy</topic><topic>Diterpenes, Abietane - chemistry</topic><topic>Diterpenes, Abietane - pharmacology</topic><topic>Endothelial Cells - drug effects</topic><topic>Endothelial Cells - metabolism</topic><topic>Endothelium</topic><topic>Free Radical Scavengers - metabolism</topic><topic>Humans</topic><topic>Hyperglycemia</topic><topic>Intracellular</topic><topic>Localization</topic><topic>Lysis</topic><topic>Microvessels - pathology</topic><topic>Molecular Docking Simulation</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Nitric Oxide - metabolism</topic><topic>Oxidative stress</topic><topic>Proteins</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Sulfonic Acids - metabolism</topic><topic>tert-Butylhydroperoxide</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Xi</creatorcontrib><creatorcontrib>Zhang, Qiao</creatorcontrib><creatorcontrib>Hou, Ning</creatorcontrib><creatorcontrib>Li, Jing</creatorcontrib><creatorcontrib>Liu, Min</creatorcontrib><creatorcontrib>Peng, Sha</creatorcontrib><creatorcontrib>Zhang, Yuxin</creatorcontrib><creatorcontrib>Luo, Yinzhen</creatorcontrib><creatorcontrib>Zhao, Bowen</creatorcontrib><creatorcontrib>Wang, Shifeng</creatorcontrib><creatorcontrib>Zhang, Yanling</creatorcontrib><creatorcontrib>Qiao, Yanjiang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Xi</au><au>Zhang, Qiao</au><au>Hou, Ning</au><au>Li, Jing</au><au>Liu, Min</au><au>Peng, Sha</au><au>Zhang, Yuxin</au><au>Luo, Yinzhen</au><au>Zhao, Bowen</au><au>Wang, Shifeng</au><au>Zhang, Yanling</au><au>Qiao, Yanjiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Carnosol as a Nrf2 Activator Improves Endothelial Barrier Function Through Antioxidative Mechanisms</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2019-02-18</date><risdate>2019</risdate><volume>20</volume><issue>4</issue><spage>880</spage><pages>880-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Oxidative stress is the main pathogenesis of diabetic microangiopathy, which can cause microvascular endothelial cell damage and destroy vascular barrier. In this study, it is found that carnosol protects human microvascular endothelial cells (HMVEC) through antioxidative mechanisms. First, we measured the antioxidant activity of carnosol. We showed that carnosol pretreatment suppressed tert-butyl hydroperoxide (t-BHP)-induced cell viability, affected the production of lactate dehydrogenase (LDH) as well as reactive oxygen species (ROS), and increased the produce of nitric oxide (NO). Additionally, carnosol promotes the protein expression of vascular endothelial cadherin (VE-cadherin) to keep the integrity of intercellular junctions, which indicated that it protected microvascular barrier in oxidative stress. Meanwhile, we investigated that carnosol can interrupt Nrf2-Keap1 protein-protein interaction and stimulated antioxidant-responsive element (ARE)-driven luciferase activity in vitro. Mechanistically, we showed that carnosol promotes the expression of heme oxygenase 1(HO-1) and nuclear factor-erythroid 2 related factor 2(Nrf2). It can also promote the expression of endothelial nitric oxide synthase (eNOS). Collectively, our data support the notion that carnosol is a protective agent in HMVECs and has the potential for therapeutic use in the treatments of microvascular endothelial cell injury.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>30781644</pmid><doi>10.3390/ijms20040880</doi><orcidid>https://orcid.org/0000-0002-4999-8436</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Antigens, CD - metabolism Antioxidants Antioxidants - pharmacology Apoptosis Benzothiazoles - metabolism Cadherins - metabolism Cell injury Cell Line Cell membranes Cytoprotection - drug effects Cytoprotection - genetics Cytotoxicity Diabetes Diabetes mellitus Diabetic neuropathy Diabetic retinopathy Diterpenes, Abietane - chemistry Diterpenes, Abietane - pharmacology Endothelial Cells - drug effects Endothelial Cells - metabolism Endothelium Free Radical Scavengers - metabolism Humans Hyperglycemia Intracellular Localization Lysis Microvessels - pathology Molecular Docking Simulation NF-E2-Related Factor 2 - metabolism Nitric Oxide - metabolism Oxidative stress Proteins Reactive Oxygen Species - metabolism Sulfonic Acids - metabolism tert-Butylhydroperoxide |
| title | Carnosol as a Nrf2 Activator Improves Endothelial Barrier Function Through Antioxidative Mechanisms |
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