Schisandrin B Protects against Acute Ethanol-Induced Cardiac Injury by Downregulating Autophagy via the NOX4/ROS Pathway
Introduction: Although oxidative stress has been demonstrated to mediate acute ethanol-induced changes in autophagy in the heart, the precise mechanism behind redox regulation in acute ethanol heart disease remains largely unknown. Methods: Wild-type C57BL/6 mice were intraperitoneally injected with...
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| Veröffentlicht in: | Pharmacology 2021-03, Vol.106 (3-4), p.177-188 |
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| creator | Tao, Youli Zhou, Hua Huang, Lili Xu, Xiaoyin Huang, Yun Ma, Lili Li, Lingna Yao, Xu Zhang, Ronghui Zhang, Yuyu Rong, Weibo Yang, Chaojun Yang, Taotao Shen, Yi Wang, Rixiang |
| description | Introduction: Although oxidative stress has been demonstrated to mediate acute ethanol-induced changes in autophagy in the heart, the precise mechanism behind redox regulation in acute ethanol heart disease remains largely unknown. Methods: Wild-type C57BL/6 mice were intraperitoneally injected with ethanol (3 g/kg/day) for 3 consecutive days. The effects of ethanol on cultured primary cardiomyocytes and H9c2 myoblasts were also studied in vitro. Levels of autophagic flux, cardiac apoptosis and function, reactive oxygen species (ROS) accumulation, NOX4, and NOX2 were examined. The NOX4 gene was knocked down with NOX4 siRNA. Results: In this study, we demonstrated that schisandrin B inhibited acute ethanol-induced autophagy and sequent apoptosis. In addition, schisandrin B treatment improved cardiac function in ethanol-treated mice. Furthermore, NOX4 protein expression was increased during acute ethanol exposure, and the upregulation of NOX4 was significantly inhibited by schisandrin B treatment. The knockdown of NOX4 prevented ROS accumulation, cell autophagy, and apoptosis. Conclusion: These results highlight that NOX4 is a critical mediator of ROS and elaborate the role of the NOX4/ROS axis in the effect of schisandrin B on autophagy and autophagy-mediated apoptosis in acute ethanol exposure, which suggests a therapeutic strategy for acute alcoholic cardiomyopathy. |
| doi_str_mv | 10.1159/000510863 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1159_000510863</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A698026806</galeid><sourcerecordid>A698026806</sourcerecordid><originalsourceid>FETCH-LOGICAL-c373t-503b3c195051799c38306acb651b31cbf05b4e86325c7c5a8c34a69af03cdb213</originalsourceid><addsrcrecordid>eNpt0c9r2zAUB3BRVto022H3MQQ79eBWsmzZPmZZfwTKEtoOdjPPz7KtLpGDJK_1f1-VtIFC0eGB-HwfPL6EfOXsjPO0OGeMpZzlUhyQCU9iETHBxScyYWFGGePxMTlx7iEwGWf5ETkWIsllkscT8nSHnXZgaqsN_UlXtvcKvaPQgjbO0xkOXtEL34Hp19HC1AOqms7B1hqQLszDYEdajfRX_2isaoc1eG1aOht8v-2gHel_DdR3iv5e_k3Ob5d3dAW-e4TxMzlsYO3Ul9c5JX8uL-7n19HN8moxn91EKDLho5SJSiAv0nBhVhQocsEkYCVTXgmOVcPSKlHh9DjFDFPIUSQgC2iYwLqKuZiSH7u9LaxVqU3Tewu40Q7LmSxyFsucyaDOPlDh1WqjsTeq0eH_XeB0F0DbO2dVU26t3oAdS87Kl1LKfSnBft_Z7VBtVL2Xby0E8G0H_oFtld2D1_wzg3yOEg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Schisandrin B Protects against Acute Ethanol-Induced Cardiac Injury by Downregulating Autophagy via the NOX4/ROS Pathway</title><source>MEDLINE</source><source>Karger Journals</source><creator>Tao, Youli ; Zhou, Hua ; Huang, Lili ; Xu, Xiaoyin ; Huang, Yun ; Ma, Lili ; Li, Lingna ; Yao, Xu ; Zhang, Ronghui ; Zhang, Yuyu ; Rong, Weibo ; Yang, Chaojun ; Yang, Taotao ; Shen, Yi ; Wang, Rixiang</creator><creatorcontrib>Tao, Youli ; Zhou, Hua ; Huang, Lili ; Xu, Xiaoyin ; Huang, Yun ; Ma, Lili ; Li, Lingna ; Yao, Xu ; Zhang, Ronghui ; Zhang, Yuyu ; Rong, Weibo ; Yang, Chaojun ; Yang, Taotao ; Shen, Yi ; Wang, Rixiang</creatorcontrib><description>Introduction: Although oxidative stress has been demonstrated to mediate acute ethanol-induced changes in autophagy in the heart, the precise mechanism behind redox regulation in acute ethanol heart disease remains largely unknown. Methods: Wild-type C57BL/6 mice were intraperitoneally injected with ethanol (3 g/kg/day) for 3 consecutive days. The effects of ethanol on cultured primary cardiomyocytes and H9c2 myoblasts were also studied in vitro. Levels of autophagic flux, cardiac apoptosis and function, reactive oxygen species (ROS) accumulation, NOX4, and NOX2 were examined. The NOX4 gene was knocked down with NOX4 siRNA. Results: In this study, we demonstrated that schisandrin B inhibited acute ethanol-induced autophagy and sequent apoptosis. In addition, schisandrin B treatment improved cardiac function in ethanol-treated mice. Furthermore, NOX4 protein expression was increased during acute ethanol exposure, and the upregulation of NOX4 was significantly inhibited by schisandrin B treatment. The knockdown of NOX4 prevented ROS accumulation, cell autophagy, and apoptosis. Conclusion: These results highlight that NOX4 is a critical mediator of ROS and elaborate the role of the NOX4/ROS axis in the effect of schisandrin B on autophagy and autophagy-mediated apoptosis in acute ethanol exposure, which suggests a therapeutic strategy for acute alcoholic cardiomyopathy.</description><identifier>ISSN: 0031-7012</identifier><identifier>EISSN: 1423-0313</identifier><identifier>DOI: 10.1159/000510863</identifier><identifier>PMID: 33486482</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Acetaldehyde ; Alcohol ; Alcohol, Denatured ; Animals ; Apoptosis ; Apoptosis - drug effects ; Autophagy - drug effects ; Autophagy - genetics ; Cardiomyopathy, Alcoholic - prevention & control ; Cyclooctanes - pharmacology ; Cyclooctanes - therapeutic use ; Down-Regulation ; Ethanol - toxicity ; Gene Knockdown Techniques ; Heart ; Heart diseases ; Heart Injuries - chemically induced ; Heart Injuries - metabolism ; Heart Injuries - prevention & control ; Lignans - pharmacology ; Lignans - therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - pathology ; NADPH Oxidase 4 - antagonists & inhibitors ; NADPH Oxidase 4 - genetics ; NADPH Oxidase 4 - metabolism ; Photographic industry ; Polycyclic Compounds - pharmacology ; Polycyclic Compounds - therapeutic use ; Primary Cell Culture ; Protective Agents - pharmacology ; Protective Agents - therapeutic use ; Reactive Oxygen Species - antagonists & inhibitors ; Reactive Oxygen Species - metabolism ; Research Article ; Signal Transduction - drug effects</subject><ispartof>Pharmacology, 2021-03, Vol.106 (3-4), p.177-188</ispartof><rights>2021 S. Karger AG, Basel</rights><rights>2021 S. Karger AG, Basel.</rights><rights>COPYRIGHT 2021 S. Karger AG</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c373t-503b3c195051799c38306acb651b31cbf05b4e86325c7c5a8c34a69af03cdb213</citedby><cites>FETCH-LOGICAL-c373t-503b3c195051799c38306acb651b31cbf05b4e86325c7c5a8c34a69af03cdb213</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2427,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33486482$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tao, Youli</creatorcontrib><creatorcontrib>Zhou, Hua</creatorcontrib><creatorcontrib>Huang, Lili</creatorcontrib><creatorcontrib>Xu, Xiaoyin</creatorcontrib><creatorcontrib>Huang, Yun</creatorcontrib><creatorcontrib>Ma, Lili</creatorcontrib><creatorcontrib>Li, Lingna</creatorcontrib><creatorcontrib>Yao, Xu</creatorcontrib><creatorcontrib>Zhang, Ronghui</creatorcontrib><creatorcontrib>Zhang, Yuyu</creatorcontrib><creatorcontrib>Rong, Weibo</creatorcontrib><creatorcontrib>Yang, Chaojun</creatorcontrib><creatorcontrib>Yang, Taotao</creatorcontrib><creatorcontrib>Shen, Yi</creatorcontrib><creatorcontrib>Wang, Rixiang</creatorcontrib><title>Schisandrin B Protects against Acute Ethanol-Induced Cardiac Injury by Downregulating Autophagy via the NOX4/ROS Pathway</title><title>Pharmacology</title><addtitle>Pharmacology</addtitle><description>Introduction: Although oxidative stress has been demonstrated to mediate acute ethanol-induced changes in autophagy in the heart, the precise mechanism behind redox regulation in acute ethanol heart disease remains largely unknown. Methods: Wild-type C57BL/6 mice were intraperitoneally injected with ethanol (3 g/kg/day) for 3 consecutive days. The effects of ethanol on cultured primary cardiomyocytes and H9c2 myoblasts were also studied in vitro. Levels of autophagic flux, cardiac apoptosis and function, reactive oxygen species (ROS) accumulation, NOX4, and NOX2 were examined. The NOX4 gene was knocked down with NOX4 siRNA. Results: In this study, we demonstrated that schisandrin B inhibited acute ethanol-induced autophagy and sequent apoptosis. In addition, schisandrin B treatment improved cardiac function in ethanol-treated mice. Furthermore, NOX4 protein expression was increased during acute ethanol exposure, and the upregulation of NOX4 was significantly inhibited by schisandrin B treatment. The knockdown of NOX4 prevented ROS accumulation, cell autophagy, and apoptosis. Conclusion: These results highlight that NOX4 is a critical mediator of ROS and elaborate the role of the NOX4/ROS axis in the effect of schisandrin B on autophagy and autophagy-mediated apoptosis in acute ethanol exposure, which suggests a therapeutic strategy for acute alcoholic cardiomyopathy.</description><subject>Acetaldehyde</subject><subject>Alcohol</subject><subject>Alcohol, Denatured</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Autophagy - drug effects</subject><subject>Autophagy - genetics</subject><subject>Cardiomyopathy, Alcoholic - prevention & control</subject><subject>Cyclooctanes - pharmacology</subject><subject>Cyclooctanes - therapeutic use</subject><subject>Down-Regulation</subject><subject>Ethanol - toxicity</subject><subject>Gene Knockdown Techniques</subject><subject>Heart</subject><subject>Heart diseases</subject><subject>Heart Injuries - chemically induced</subject><subject>Heart Injuries - metabolism</subject><subject>Heart Injuries - prevention & control</subject><subject>Lignans - pharmacology</subject><subject>Lignans - therapeutic use</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - pathology</subject><subject>NADPH Oxidase 4 - antagonists & inhibitors</subject><subject>NADPH Oxidase 4 - genetics</subject><subject>NADPH Oxidase 4 - metabolism</subject><subject>Photographic industry</subject><subject>Polycyclic Compounds - pharmacology</subject><subject>Polycyclic Compounds - therapeutic use</subject><subject>Primary Cell Culture</subject><subject>Protective Agents - pharmacology</subject><subject>Protective Agents - therapeutic use</subject><subject>Reactive Oxygen Species - antagonists & inhibitors</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Research Article</subject><subject>Signal Transduction - drug effects</subject><issn>0031-7012</issn><issn>1423-0313</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0c9r2zAUB3BRVto022H3MQQ79eBWsmzZPmZZfwTKEtoOdjPPz7KtLpGDJK_1f1-VtIFC0eGB-HwfPL6EfOXsjPO0OGeMpZzlUhyQCU9iETHBxScyYWFGGePxMTlx7iEwGWf5ETkWIsllkscT8nSHnXZgaqsN_UlXtvcKvaPQgjbO0xkOXtEL34Hp19HC1AOqms7B1hqQLszDYEdajfRX_2isaoc1eG1aOht8v-2gHel_DdR3iv5e_k3Ob5d3dAW-e4TxMzlsYO3Ul9c5JX8uL-7n19HN8moxn91EKDLho5SJSiAv0nBhVhQocsEkYCVTXgmOVcPSKlHh9DjFDFPIUSQgC2iYwLqKuZiSH7u9LaxVqU3Tewu40Q7LmSxyFsucyaDOPlDh1WqjsTeq0eH_XeB0F0DbO2dVU26t3oAdS87Kl1LKfSnBft_Z7VBtVL2Xby0E8G0H_oFtld2D1_wzg3yOEg</recordid><startdate>20210301</startdate><enddate>20210301</enddate><creator>Tao, Youli</creator><creator>Zhou, Hua</creator><creator>Huang, Lili</creator><creator>Xu, Xiaoyin</creator><creator>Huang, Yun</creator><creator>Ma, Lili</creator><creator>Li, Lingna</creator><creator>Yao, Xu</creator><creator>Zhang, Ronghui</creator><creator>Zhang, Yuyu</creator><creator>Rong, Weibo</creator><creator>Yang, Chaojun</creator><creator>Yang, Taotao</creator><creator>Shen, Yi</creator><creator>Wang, Rixiang</creator><general>S. Karger AG</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></search><sort><creationdate>20210301</creationdate><title>Schisandrin B Protects against Acute Ethanol-Induced Cardiac Injury by Downregulating Autophagy via the NOX4/ROS Pathway</title><author>Tao, Youli ; Zhou, Hua ; Huang, Lili ; Xu, Xiaoyin ; Huang, Yun ; Ma, Lili ; Li, Lingna ; Yao, Xu ; Zhang, Ronghui ; Zhang, Yuyu ; Rong, Weibo ; Yang, Chaojun ; Yang, Taotao ; Shen, Yi ; Wang, Rixiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c373t-503b3c195051799c38306acb651b31cbf05b4e86325c7c5a8c34a69af03cdb213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acetaldehyde</topic><topic>Alcohol</topic><topic>Alcohol, Denatured</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Autophagy - drug effects</topic><topic>Autophagy - genetics</topic><topic>Cardiomyopathy, Alcoholic - prevention & control</topic><topic>Cyclooctanes - pharmacology</topic><topic>Cyclooctanes - therapeutic use</topic><topic>Down-Regulation</topic><topic>Ethanol - toxicity</topic><topic>Gene Knockdown Techniques</topic><topic>Heart</topic><topic>Heart diseases</topic><topic>Heart Injuries - chemically induced</topic><topic>Heart Injuries - metabolism</topic><topic>Heart Injuries - prevention & control</topic><topic>Lignans - pharmacology</topic><topic>Lignans - therapeutic use</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Myocytes, Cardiac - pathology</topic><topic>NADPH Oxidase 4 - antagonists & inhibitors</topic><topic>NADPH Oxidase 4 - genetics</topic><topic>NADPH Oxidase 4 - metabolism</topic><topic>Photographic industry</topic><topic>Polycyclic Compounds - pharmacology</topic><topic>Polycyclic Compounds - therapeutic use</topic><topic>Primary Cell Culture</topic><topic>Protective Agents - pharmacology</topic><topic>Protective Agents - therapeutic use</topic><topic>Reactive Oxygen Species - antagonists & inhibitors</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Research Article</topic><topic>Signal Transduction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tao, Youli</creatorcontrib><creatorcontrib>Zhou, Hua</creatorcontrib><creatorcontrib>Huang, Lili</creatorcontrib><creatorcontrib>Xu, Xiaoyin</creatorcontrib><creatorcontrib>Huang, Yun</creatorcontrib><creatorcontrib>Ma, Lili</creatorcontrib><creatorcontrib>Li, Lingna</creatorcontrib><creatorcontrib>Yao, Xu</creatorcontrib><creatorcontrib>Zhang, Ronghui</creatorcontrib><creatorcontrib>Zhang, Yuyu</creatorcontrib><creatorcontrib>Rong, Weibo</creatorcontrib><creatorcontrib>Yang, Chaojun</creatorcontrib><creatorcontrib>Yang, Taotao</creatorcontrib><creatorcontrib>Shen, Yi</creatorcontrib><creatorcontrib>Wang, Rixiang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tao, Youli</au><au>Zhou, Hua</au><au>Huang, Lili</au><au>Xu, Xiaoyin</au><au>Huang, Yun</au><au>Ma, Lili</au><au>Li, Lingna</au><au>Yao, Xu</au><au>Zhang, Ronghui</au><au>Zhang, Yuyu</au><au>Rong, Weibo</au><au>Yang, Chaojun</au><au>Yang, Taotao</au><au>Shen, Yi</au><au>Wang, Rixiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Schisandrin B Protects against Acute Ethanol-Induced Cardiac Injury by Downregulating Autophagy via the NOX4/ROS Pathway</atitle><jtitle>Pharmacology</jtitle><addtitle>Pharmacology</addtitle><date>2021-03-01</date><risdate>2021</risdate><volume>106</volume><issue>3-4</issue><spage>177</spage><epage>188</epage><pages>177-188</pages><issn>0031-7012</issn><eissn>1423-0313</eissn><abstract>Introduction: Although oxidative stress has been demonstrated to mediate acute ethanol-induced changes in autophagy in the heart, the precise mechanism behind redox regulation in acute ethanol heart disease remains largely unknown. Methods: Wild-type C57BL/6 mice were intraperitoneally injected with ethanol (3 g/kg/day) for 3 consecutive days. The effects of ethanol on cultured primary cardiomyocytes and H9c2 myoblasts were also studied in vitro. Levels of autophagic flux, cardiac apoptosis and function, reactive oxygen species (ROS) accumulation, NOX4, and NOX2 were examined. The NOX4 gene was knocked down with NOX4 siRNA. Results: In this study, we demonstrated that schisandrin B inhibited acute ethanol-induced autophagy and sequent apoptosis. In addition, schisandrin B treatment improved cardiac function in ethanol-treated mice. Furthermore, NOX4 protein expression was increased during acute ethanol exposure, and the upregulation of NOX4 was significantly inhibited by schisandrin B treatment. The knockdown of NOX4 prevented ROS accumulation, cell autophagy, and apoptosis. Conclusion: These results highlight that NOX4 is a critical mediator of ROS and elaborate the role of the NOX4/ROS axis in the effect of schisandrin B on autophagy and autophagy-mediated apoptosis in acute ethanol exposure, which suggests a therapeutic strategy for acute alcoholic cardiomyopathy.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>33486482</pmid><doi>10.1159/000510863</doi><tpages>12</tpages></addata></record> |
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| subjects | Acetaldehyde Alcohol Alcohol, Denatured Animals Apoptosis Apoptosis - drug effects Autophagy - drug effects Autophagy - genetics Cardiomyopathy, Alcoholic - prevention & control Cyclooctanes - pharmacology Cyclooctanes - therapeutic use Down-Regulation Ethanol - toxicity Gene Knockdown Techniques Heart Heart diseases Heart Injuries - chemically induced Heart Injuries - metabolism Heart Injuries - prevention & control Lignans - pharmacology Lignans - therapeutic use Male Mice Mice, Inbred C57BL Myocytes, Cardiac - drug effects Myocytes, Cardiac - pathology NADPH Oxidase 4 - antagonists & inhibitors NADPH Oxidase 4 - genetics NADPH Oxidase 4 - metabolism Photographic industry Polycyclic Compounds - pharmacology Polycyclic Compounds - therapeutic use Primary Cell Culture Protective Agents - pharmacology Protective Agents - therapeutic use Reactive Oxygen Species - antagonists & inhibitors Reactive Oxygen Species - metabolism Research Article Signal Transduction - drug effects |
| title | Schisandrin B Protects against Acute Ethanol-Induced Cardiac Injury by Downregulating Autophagy via the NOX4/ROS Pathway |
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