期刊文献+

地骨皮甲素对鱼藤酮诱导的PC12细胞损伤的保护作用 认领

Neuroprotective effects of kukoamine A against rotenone-induced neurotoxicity in PC12 cells
收藏 分享 导出
摘要 目的考察地骨皮甲素(kukoamine A,KuA)对鱼藤酮诱导的PC12细胞损伤的保护作用并对其作用机制进行初步研究,为发现具有抗帕金森病的活性先导化合物提供依据。方法通过体外建立鱼藤酮诱导的帕金森模型,运用MTT、LDH、Hoechst33342染色等方法对Ku A体外抗鱼藤酮诱导的PC12细胞损伤进行初步确认。利用比色法和荧光染色分别考察KuA对超氧化物歧化酶(SOD)活性、丙二醛(MDA)及活性氧(ROS)含量、线粒体膜电位(MMP)的影响。采用Western blotting探讨KuA体外抗鱼藤酮诱导PC12细胞损伤的作用机制。结果 0.5μmol/L鱼藤酮可降低PC12细胞存活率,不同浓度Ku A可减轻鱼藤酮诱导的PC12细胞损伤。与模型组相比,KuA可降低细胞内ROS及MDA含量,并提高SOD活性。此外,KuA可提高基质金属蛋白酶(MMP)水平,下调Bax/Bcl-2值、抑制细胞色素C释放以及下调Caspase-3、Caspase-9、α-synuclein的蛋白表达。结论 KuA对鱼藤酮诱导的PC12细胞帕金森病模型具有保护作用,其可能的机制与抑制ROS生成、保护MMP、调控线粒体凋亡途径相关蛋白表达和降低α-synuclein蛋白表达有关。 Objective To investigate the neuroprotective effects of kukoamine A(KuA) on rotenone-induced PC12 cells damage and to preliminary verify its potential action mechanisms. The present study may lay the foundation for finding leading compounds with anti-Parkinson’s disease(PD) effects. Methods A PD model induced by rotenone was established in vitro, and MTT, LDH, and Hoechst33342 staining were used for preliminary confirmation of KuA resistance to rotenone-induced PC12 cell injury in vitro. The effects of KuA on superoxide dismutase(SOD) activity, malondialdehyde(MDA) and reactive oxygen species(ROS) content, and mitochondrial membrane potential(MMP) were investigated by colorimetric method and fluorescence staining, respectively. Western blotting was applied to explore the underlying mechanisms of protective effects of KuA against rotenone-induced PC12 cells damage. Results The PC12 cell viability was significantly decreased after exposure to 0.5 μmol/L rotenone, whereas pretreatment with different concentrations of KuA could attenuate the cell injury induced by rotenone. Compared with the rotenone-treated group, KuA could decrease the ROS production and MDA level, while increase the SOD activity. In addition, KuA could effectively increase the MMP, decrease the cytochrome c release and the Bax/Bcl-2 ratio as well as inhibit caspase-3, caspase-9, and α-synuclein protein expressions. Conclusion KuA showed neuroprotective ability on rotenone-induced PC12 cells PD model and the potential protective mechanisms of KuA can be related with inhibition of ROS generation, protection of MMP, regulation of protein expressions involved in the mitochondrial apoptosis pathway and reduction of α-synuclein expression.
作者 刘文武 宋琪 祖宇欣 蒋晓文 杨玥 高欢 赵庆春 LIU Wen-wu;SONG Qi;ZU Yu-xin;JIANG Xiao-wen;YANG Yue;GAO Huan;ZHAO Qing-chun(Department of Pharmacy,General Hospital of Northern Theater Command,Shenyang 110840,China;Shenyang Pharmaceutical University,Shenyang 110016,China)
出处 《中草药》 CAS CSCD 北大核心 2020年第24期6302-6309,共8页 Chinese Traditional and Herbal Drugs
基金 国家科技重大专项:新概念武器损伤防治药物SZ516的研究(2014ZX09J14101-05C) 国家自然科学基金资助项目(81673328,81973209)。
关键词 地骨皮甲素 鱼藤酮 PC12细胞 帕金森病 线粒体凋亡途径 活性氧 kukoamine A rotenone PC12 cells Parkinson’s disease mitochondrial apoptosis pathway reactive oxygen
  • 相关文献

参考文献1

二级参考文献36

  • 1Citron BA,Suo Z,SantaCruz K,et al.Protein crosslinking,tissue transglutaminase,alternative splicing and neurodegeneration.Neurochem Int.2002;40(1):69-78. 被引量:1
  • 2Mindermann T,Landolt H,Zimmerli W,et al.Penetration of rifampicin into the brain tissue and cerebral extracellular space of rats.J Antimicrob Chemother.1993;31(5):731-737. 被引量:1
  • 3Yulug B,Kilic U,Kilic E,et al.Rifampicin attenuates brain damage in focal ischemia.Brain Res.2004;996(1):76-80. 被引量:1
  • 4Tomiyama T,Kaneko H,Kataoka K,et al.Rifampicin inhibits the toxicity of pre-aggregated amyloid peptides by binding to peptide fibrils and preventing amyloid-cell interaction.Biochem J.1997; 322(Pt 3):859-865. 被引量:1
  • 5Zhu M,Rajamani S,Kaylor J,et al.The flavonoid baicalein inhibits fibrillation of alpha-synuclein and disaggregates existing fibrils.J Biol Chem.2004;279(26):26846-26857. 被引量:1
  • 6Conway KA,Rochet JC,Bieganski RM,et al.Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct.Science.2001;294(5545):1346-1349. 被引量:1
  • 7Calleja C,Pascussi JM,Mani JC,et al.The antibiotic rifampicin is a nonsteroidal ligand and activator of the human glucocorticoid receptor.Nat Med.1998;4(1):92-96. 被引量:1
  • 8Gollapudi S,Jaidka S,Gupta S.Molecular basis of rifampicin-induced inhibition of anti-CD95-induced apoptosis of peripheral blood T lymphocytes:the role of CD95 ligand and FLIPs.J Clin Immunol.2003;23(1):11-22. 被引量:1
  • 9Herr AS,Wochnik GM,Rosenhagen MC,et al.Rifampicin is not an activator of glucocorticoid receptor.Mol Pharmacol.2000;57(4):732-737. 被引量:1
  • 10Shults CW. Lewy bodies. Proc Natl Acad Sci U S A. 2006;103(6): 1661-1668. 被引量:1

共引文献1

维普数据出版直通车
今日学术
投稿分析
职称考试

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部 意见反馈