Neuroprotective Effect of Ginkgolide B on Bupivacaine-Induced Apoptosis in SH-SY5Y Cells
Local anesthetics are used routinely and effectively. However, many are also known to activate neurotoxic pathways. We tested the neuroprotective efficacy of ginkgolide B (GB), an active component of Ginkgo biloba, against ROS-mediated neurotoxicity caused by the local anesthetic bupivacaine. SH-SY5...
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| Veröffentlicht in: | Oxidative medicine and cellular longevity 2013-01, Vol.2013 (2013), p.1-11 |
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| creator | Xu, Shi-yuan Cheung, Chi-wai Zheng, Ting Zhou, Shu-qin Wen, Xian-jie Lai, Lu-ying Li, Le Zhang, Qing-guo |
| description | Local anesthetics are used routinely and effectively. However, many are also known to activate neurotoxic pathways. We tested the neuroprotective efficacy of ginkgolide B (GB), an active component of Ginkgo biloba, against ROS-mediated neurotoxicity caused by the local anesthetic bupivacaine. SH-SY5Y cells were treated with different concentrations of bupivacaine alone or following preincubation with GB. Pretreatment with GB increased SH-SY5Y cell viability and attenuated intracellular ROS accumulation, apoptosis, mitochondrial dysfunction, and ER stress. GB suppressed bupivacaine-induced mitochondrial depolarization and mitochondria complex I and III inhibition and increased cleaved caspase-3 and Htra2 expression, which was strongly indicative of activation of mitochondria-dependent apoptosis with concomitantly enhanced expressions of Grp78, caspase-12 mRNA, protein, and ER stress. GB also improved ultrastructural changes indicative of mitochondrial and ER damage induced by bupivacaine. These results implicate bupivacaine-induced ROS-dependent mitochondria, ER dysfunction, and apoptosis, which can be attenuated by GB through its antioxidant property. |
| doi_str_mv | 10.1155/2013/159864 |
| format | Article |
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However, many are also known to activate neurotoxic pathways. We tested the neuroprotective efficacy of ginkgolide B (GB), an active component of Ginkgo biloba, against ROS-mediated neurotoxicity caused by the local anesthetic bupivacaine. SH-SY5Y cells were treated with different concentrations of bupivacaine alone or following preincubation with GB. Pretreatment with GB increased SH-SY5Y cell viability and attenuated intracellular ROS accumulation, apoptosis, mitochondrial dysfunction, and ER stress. GB suppressed bupivacaine-induced mitochondrial depolarization and mitochondria complex I and III inhibition and increased cleaved caspase-3 and Htra2 expression, which was strongly indicative of activation of mitochondria-dependent apoptosis with concomitantly enhanced expressions of Grp78, caspase-12 mRNA, protein, and ER stress. GB also improved ultrastructural changes indicative of mitochondrial and ER damage induced by bupivacaine. These results implicate bupivacaine-induced ROS-dependent mitochondria, ER dysfunction, and apoptosis, which can be attenuated by GB through its antioxidant property.</description><identifier>ISSN: 1942-0900</identifier><identifier>EISSN: 1942-0994</identifier><identifier>DOI: 10.1155/2013/159864</identifier><identifier>PMID: 24228138</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Puplishing Corporation</publisher><subject>Apoptosis - drug effects ; Bupivacaine - toxicity ; Caspase 12 - genetics ; Caspase 12 - metabolism ; Caspase 3 - metabolism ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell Shape - drug effects ; Cell Shape - genetics ; Cell Survival - drug effects ; Cell Survival - genetics ; Electron Transport Complex I - metabolism ; Electron Transport Complex III - metabolism ; Endoplasmic Reticulum Stress - drug effects ; Endoplasmic Reticulum Stress - genetics ; Enzyme Activation - drug effects ; Flow Cytometry ; Ginkgolides - pharmacology ; Heat-Shock Proteins - genetics ; Heat-Shock Proteins - metabolism ; High-Temperature Requirement A Serine Peptidase 2 ; Humans ; Lactones - pharmacology ; Membrane Potential, Mitochondrial - drug effects ; Membrane Potential, Mitochondrial - genetics ; Mitochondria - drug effects ; Mitochondria - metabolism ; Mitochondria - ultrastructure ; Mitochondrial Proteins - metabolism ; Neuroprotective Agents - pharmacology ; Reactive Oxygen Species - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Serine Endopeptidases - metabolism</subject><ispartof>Oxidative medicine and cellular longevity, 2013-01, Vol.2013 (2013), p.1-11</ispartof><rights>Copyright © 2013 Le Li et al.</rights><rights>Copyright © 2013 Le Li et al. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-2123bff0b8bdadb77bff13f3ab01b1df9d463b1d9fef95fd09b9b1945a92a913</citedby><cites>FETCH-LOGICAL-c438t-2123bff0b8bdadb77bff13f3ab01b1df9d463b1d9fef95fd09b9b1945a92a913</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3818975/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3818975/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24228138$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Xia, Zhengyuan</contributor><creatorcontrib>Xu, Shi-yuan</creatorcontrib><creatorcontrib>Cheung, Chi-wai</creatorcontrib><creatorcontrib>Zheng, Ting</creatorcontrib><creatorcontrib>Zhou, Shu-qin</creatorcontrib><creatorcontrib>Wen, Xian-jie</creatorcontrib><creatorcontrib>Lai, Lu-ying</creatorcontrib><creatorcontrib>Li, Le</creatorcontrib><creatorcontrib>Zhang, Qing-guo</creatorcontrib><title>Neuroprotective Effect of Ginkgolide B on Bupivacaine-Induced Apoptosis in SH-SY5Y Cells</title><title>Oxidative medicine and cellular longevity</title><addtitle>Oxid Med Cell Longev</addtitle><description>Local anesthetics are used routinely and effectively. However, many are also known to activate neurotoxic pathways. We tested the neuroprotective efficacy of ginkgolide B (GB), an active component of Ginkgo biloba, against ROS-mediated neurotoxicity caused by the local anesthetic bupivacaine. SH-SY5Y cells were treated with different concentrations of bupivacaine alone or following preincubation with GB. Pretreatment with GB increased SH-SY5Y cell viability and attenuated intracellular ROS accumulation, apoptosis, mitochondrial dysfunction, and ER stress. GB suppressed bupivacaine-induced mitochondrial depolarization and mitochondria complex I and III inhibition and increased cleaved caspase-3 and Htra2 expression, which was strongly indicative of activation of mitochondria-dependent apoptosis with concomitantly enhanced expressions of Grp78, caspase-12 mRNA, protein, and ER stress. GB also improved ultrastructural changes indicative of mitochondrial and ER damage induced by bupivacaine. These results implicate bupivacaine-induced ROS-dependent mitochondria, ER dysfunction, and apoptosis, which can be attenuated by GB through its antioxidant property.</description><subject>Apoptosis - drug effects</subject><subject>Bupivacaine - toxicity</subject><subject>Caspase 12 - genetics</subject><subject>Caspase 12 - metabolism</subject><subject>Caspase 3 - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Shape - drug effects</subject><subject>Cell Shape - genetics</subject><subject>Cell Survival - drug effects</subject><subject>Cell Survival - genetics</subject><subject>Electron Transport Complex I - metabolism</subject><subject>Electron Transport Complex III - metabolism</subject><subject>Endoplasmic Reticulum Stress - drug effects</subject><subject>Endoplasmic Reticulum Stress - genetics</subject><subject>Enzyme Activation - drug effects</subject><subject>Flow Cytometry</subject><subject>Ginkgolides - pharmacology</subject><subject>Heat-Shock Proteins - genetics</subject><subject>Heat-Shock Proteins - metabolism</subject><subject>High-Temperature Requirement A Serine Peptidase 2</subject><subject>Humans</subject><subject>Lactones - pharmacology</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Membrane Potential, Mitochondrial - genetics</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondria - ultrastructure</subject><subject>Mitochondrial Proteins - metabolism</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Serine Endopeptidases - metabolism</subject><issn>1942-0900</issn><issn>1942-0994</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><recordid>eNqFkM1PAjEQxRujEURPnjU9a1b6sYXtxQQIAgnRAxzktGm3LVSXdrMfGP97l6xu9ORp3mR-8ybzALjG6AFjxvoEYdrHjEeD8AR0MQ9JgDgPT1uNUAdcFMUbQgNKQnwOOiQkJMI06oLXZ13lPst9qZPSHjScGlMr6A2cWfe-9alVGo6hd3BcZfYgEmGdDhZOVYlWcJT5rPSFLaB1cDUPVhu2gROdpsUlODMiLfTVd-2B9dN0PZkHy5fZYjJaBklIozIgmFBpDJKRVELJ4bBuMDVUSIQlVoarcEBrwY02nBmFuOSy_osJTgTHtAceG9usknutEu3KXKRxltu9yD9jL2z8d-LsLt76Q0wjHPEhqw3uG4Mk90WRa9PuYhQf842P-cZNvjV9-_tcy_4EWgN3DbCzTokP-4_bTQPrGtFGtHDI0ABz-gUII43u</recordid><startdate>20130101</startdate><enddate>20130101</enddate><creator>Xu, Shi-yuan</creator><creator>Cheung, Chi-wai</creator><creator>Zheng, Ting</creator><creator>Zhou, Shu-qin</creator><creator>Wen, Xian-jie</creator><creator>Lai, Lu-ying</creator><creator>Li, Le</creator><creator>Zhang, Qing-guo</creator><general>Hindawi Puplishing Corporation</general><general>Hindawi Publishing Corporation</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><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>5PM</scope></search><sort><creationdate>20130101</creationdate><title>Neuroprotective Effect of Ginkgolide B on Bupivacaine-Induced Apoptosis in SH-SY5Y Cells</title><author>Xu, Shi-yuan ; Cheung, Chi-wai ; Zheng, Ting ; Zhou, Shu-qin ; Wen, Xian-jie ; Lai, Lu-ying ; Li, Le ; Zhang, Qing-guo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-2123bff0b8bdadb77bff13f3ab01b1df9d463b1d9fef95fd09b9b1945a92a913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Apoptosis - drug effects</topic><topic>Bupivacaine - toxicity</topic><topic>Caspase 12 - genetics</topic><topic>Caspase 12 - metabolism</topic><topic>Caspase 3 - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Shape - drug effects</topic><topic>Cell Shape - genetics</topic><topic>Cell Survival - drug effects</topic><topic>Cell Survival - genetics</topic><topic>Electron Transport Complex I - metabolism</topic><topic>Electron Transport Complex III - metabolism</topic><topic>Endoplasmic Reticulum Stress - drug effects</topic><topic>Endoplasmic Reticulum Stress - genetics</topic><topic>Enzyme Activation - drug effects</topic><topic>Flow Cytometry</topic><topic>Ginkgolides - pharmacology</topic><topic>Heat-Shock Proteins - genetics</topic><topic>Heat-Shock Proteins - metabolism</topic><topic>High-Temperature Requirement A Serine Peptidase 2</topic><topic>Humans</topic><topic>Lactones - pharmacology</topic><topic>Membrane Potential, Mitochondrial - drug effects</topic><topic>Membrane Potential, Mitochondrial - genetics</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Mitochondria - ultrastructure</topic><topic>Mitochondrial Proteins - metabolism</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Serine Endopeptidases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Shi-yuan</creatorcontrib><creatorcontrib>Cheung, Chi-wai</creatorcontrib><creatorcontrib>Zheng, Ting</creatorcontrib><creatorcontrib>Zhou, Shu-qin</creatorcontrib><creatorcontrib>Wen, Xian-jie</creatorcontrib><creatorcontrib>Lai, Lu-ying</creatorcontrib><creatorcontrib>Li, Le</creatorcontrib><creatorcontrib>Zhang, Qing-guo</creatorcontrib><collection>الدوريات العلمية والإحصائية - e-Marefa Academic and Statistical Periodicals</collection><collection>معرفة - المحتوى العربي الأكاديمي المتكامل - e-Marefa Academic Complete</collection><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oxidative medicine and cellular longevity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, Shi-yuan</au><au>Cheung, Chi-wai</au><au>Zheng, Ting</au><au>Zhou, Shu-qin</au><au>Wen, Xian-jie</au><au>Lai, Lu-ying</au><au>Li, Le</au><au>Zhang, Qing-guo</au><au>Xia, Zhengyuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuroprotective Effect of Ginkgolide B on Bupivacaine-Induced Apoptosis in SH-SY5Y Cells</atitle><jtitle>Oxidative medicine and cellular longevity</jtitle><addtitle>Oxid Med Cell Longev</addtitle><date>2013-01-01</date><risdate>2013</risdate><volume>2013</volume><issue>2013</issue><spage>1</spage><epage>11</epage><pages>1-11</pages><issn>1942-0900</issn><eissn>1942-0994</eissn><abstract>Local anesthetics are used routinely and effectively. However, many are also known to activate neurotoxic pathways. We tested the neuroprotective efficacy of ginkgolide B (GB), an active component of Ginkgo biloba, against ROS-mediated neurotoxicity caused by the local anesthetic bupivacaine. SH-SY5Y cells were treated with different concentrations of bupivacaine alone or following preincubation with GB. Pretreatment with GB increased SH-SY5Y cell viability and attenuated intracellular ROS accumulation, apoptosis, mitochondrial dysfunction, and ER stress. GB suppressed bupivacaine-induced mitochondrial depolarization and mitochondria complex I and III inhibition and increased cleaved caspase-3 and Htra2 expression, which was strongly indicative of activation of mitochondria-dependent apoptosis with concomitantly enhanced expressions of Grp78, caspase-12 mRNA, protein, and ER stress. GB also improved ultrastructural changes indicative of mitochondrial and ER damage induced by bupivacaine. These results implicate bupivacaine-induced ROS-dependent mitochondria, ER dysfunction, and apoptosis, which can be attenuated by GB through its antioxidant property.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Puplishing Corporation</pub><pmid>24228138</pmid><doi>10.1155/2013/159864</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Apoptosis - drug effects Bupivacaine - toxicity Caspase 12 - genetics Caspase 12 - metabolism Caspase 3 - metabolism Cell Line, Tumor Cell Proliferation - drug effects Cell Shape - drug effects Cell Shape - genetics Cell Survival - drug effects Cell Survival - genetics Electron Transport Complex I - metabolism Electron Transport Complex III - metabolism Endoplasmic Reticulum Stress - drug effects Endoplasmic Reticulum Stress - genetics Enzyme Activation - drug effects Flow Cytometry Ginkgolides - pharmacology Heat-Shock Proteins - genetics Heat-Shock Proteins - metabolism High-Temperature Requirement A Serine Peptidase 2 Humans Lactones - pharmacology Membrane Potential, Mitochondrial - drug effects Membrane Potential, Mitochondrial - genetics Mitochondria - drug effects Mitochondria - metabolism Mitochondria - ultrastructure Mitochondrial Proteins - metabolism Neuroprotective Agents - pharmacology Reactive Oxygen Species - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Serine Endopeptidases - metabolism |
| title | Neuroprotective Effect of Ginkgolide B on Bupivacaine-Induced Apoptosis in SH-SY5Y Cells |
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