Acquisition of Chemoresistance in Gliomas Is Associated with Increased Mitochondrial Coupling and Decreased ROS Production 英文参考文献.docVIP

下载本文档

3
0
约 10页
2017-05-11 发布于上海
举报
版权申诉

Acquisition of Chemoresistance in Gliomas Is Associated with Increased Mitochondrial Coupling and Decreased ROS Production 英文参考文献.doc

1、本文档共10页，可阅读全部内容。
2、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
7、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
8、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

Acquisition of Chemoresistance in Gliomas Is Associated with Increased Mitochondrial Coupling and Decreased ROS Production 英文参考文献

AcquisitionofChemoresistanceinGliomasIsAssociated withIncreasedMitochondrialCouplingandDecreased ROSProduction ClaudiaR.Oliva1,DouglasR.Moellering2,G.YanceyGillespie1,CorinneE.Griguer1,3* 1DivisionofNeurosurgery,DepartmentofSurgery,UniversityofAlabamaatBirmingham,Birmingham,Alabama,UnitedStatesofAmerica, 2DepartmentofNutrition Sciences,UniversityofAlabamaatBirmingham,Birmingham,Alabama,UnitedStatesofAmerica,3CenterforFreeRadicalBiology,UniversityofAlabamaatBirmingham, Birmingham,Alabama,UnitedStatesofAmerica Abstract Temozolomide (TMZ) is an alkylating agent used for treating gliomas. Chemoresistance is a severe limitation to TMZ therapy; there is a critical need to understand the underlying mechanisms that determine tumor response to TMZ. We recently reported that chemoresistance to TMZ is related to a remodeling of the entire electron transport chain, with significant increases in the activity of complexes II/III and cytochrome c oxidase (CcO). Moreover, pharmacologic and geneticmanipulationofCcOreverseschemoresistance.Therefore,totestthehypothesisthatTMZ-resistancearisesfrom tightermitochondrialcouplinganddecreasedproductionofreactiveoxygenspecies(ROS),wehaveassessedmitochondrial function in TMZ-sensitive and -resistant glioma cells, and in TMZ-resistant glioblastoma multiform (GBM) xenograft lines (xenolines).MaximumADP-stimulated(state3)ratesofmitochondrialoxygenconsumptionweregreaterinTMZ-resistant cells and xenolines, and basal respiration (state 2), proton leak (state 4), and mitochondrial ROS production were significantlylowerinTMZ-resistantcells.Furthermore,TMZ-resistantcellsconsumedlessglucoseandproducedlesslactic acid.ChemoresistantcellswereinsensitivetotheoxidativestressinducedbyTMZandhydrogenperoxidechallenges,but treatment with the oxidant L-buthionine-S,R-sulfoximine increased TMZ-dependent ROS generation and reversed chemoresistance.Importantly,treatmentwiththeantioxidantN-acetyl-cysteineinhibitedTMZ-dependentROSgeneration inchemosensitive