[1]李利容,傅若秋,高宁.异鼠李素-3-O-葡萄糖苷抑制MPP+诱导的PC-12细胞线粒体损伤和细胞凋亡[J].第三军医大学学报,2018,40(23):2147-2153.
 LI Lirong,FU Ruoqiu,GAO Ning.Isorhamnetin-3-o-glucoside inhibits MPP+-induced mitochondrial injury and apoptosis in PC-12 cells[J].J Third Mil Med Univ,2018,40(23):2147-2153.
点击复制

异鼠李素-3-O-葡萄糖苷抑制MPP+诱导的PC-12细胞线粒体损伤和细胞凋亡(/HTML )
分享到:

《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
40卷
期数:
2018年第23期
页码:
2147-2153
栏目:
基础医学
出版日期:
2018-12-15

文章信息/Info

Title:
Isorhamnetin-3-o-glucoside inhibits MPP+-induced mitochondrial injury and apoptosis in PC-12 cells
作者:
李利容傅若秋高宁
陆军军医大学(第三军医大学)药学与检验医学系生药学教研室
Author(s):
LI Lirong FU Ruoqiu GAO Ning

Department of Pharmacognosy, Faculty of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, China
 

关键词:
异鼠李素-3-O-葡萄糖苷帕金森病线粒体分裂细胞凋亡
Keywords:
isorhamnetin-3-O-glucoside Parkinson&rsquos disease mitochondrial fission apoptosis
分类号:
R285.5; R329.26; R724.502
文献标志码:
A
摘要:

目的探讨异鼠李素-3-O-葡萄糖苷(isorhamnetin-3-O-glucoside, IR3G)抑制MPP+诱导的PC12细胞线粒体损伤和细胞凋亡的分子机制。方法应用不同浓度MPP+作用于PC-12细胞,选取最佳浓度0.75mmol/L建立帕金森病体外细胞模型。实验分组:对照组、IR3G组、MPP+组、IR3G+MPP+组。采用MTT法测定细胞存活率;AnnexinV/PI双染和流式分析法检测细胞凋亡;Western blot检测凋亡相关蛋白PARP1、cleaved-Caspase 3、cleaved-Caspase 9以及Bcl-2、Bax、Bim的表达水平和细胞色素C(Cyto C)的释放;JC-1荧光探针流式检测线粒体膜电位;激光共聚焦显微镜观察线粒体形态的变化。结果IR3G可以明显降低MPP+对细胞活性的抑制作用,呈明显的量效关系;IR3G可明显阻断MPP+诱导的细胞凋亡[(43.59±1.57)% vs (14.93±0.82)%,P<0.01];IR3G可以阻断MPP+引起的凋亡相关蛋白PARP1的降解,Caspase 3和Caspase 9的激活以及Bcl-2的下调,Bim的上调,Bax的线粒体转位和Cyto C的释放;IR3G可以显著逆转MPP+引起的线粒体膜电位降低[(7.146±0.496)% vs (15.780±0.518)%,P<0.01];同时IR3G能够阻断MPP+诱导的线粒体分裂。结论异鼠李素-3-O-葡萄糖苷能通过抑制MPP+诱导的细胞线粒体损伤来阻断PC-12细胞凋亡。

Abstract:

ObjectiveTo explore the molecular mechanism of isorhamnetin-3-o-glucoside (IR3G) inhibiting MPP+-induced mitochondrial injury and apoptosis in PC-12 cells. MethodsPC-12 cells were treated with various concentrations of MPP+, and the optimal concentration (0.75 mmol/L) was selected to establish the Parkinson’s disease cell model in vitro. PC12 cells were treated without or with IR3G or MPP+ alone or combined together. Then MTT assay was used to detect cell viability. Cell apoptosis was measured by Annexin V/PI staining and flow cytometry. The expression of apoptosis related proteins, including PARP1, cleaved-Caspase 3, cleaved-Caspase 9, Bcl-2, Bax, Bim and release of Cyto C was determined by Western blot analysis. Mitochondrial membrane potential was detected by JC-1 staining and flow cytometry. The mitochondrial morphology was observed by confocal laser scanning microscopy. ResultsIR3G pretreatment for PC-12 cells significantly attenuated MPP+-mediated inhibition of cell viability in a dosedependent manner. IR3G pretreatment also obviously abrogated MPP+-induced apoptosis [(43.59±1.57)% vs (14.93±0.82)%, P<0.01]. In addition, IR3G also blocked the degradation of PARP1, activation of Caspase 3 and Caspase 9, down-regulation of Bcl-2, upregulation of Bim, mitochondrial translocation of Bax, and release of Cyto C induced by MPP+. IR3G reversed the decrease of mitochondrial membrane potential induced by MPP+ [(7.146±0.496)% vs (15.780±0.518)%,P<0.01]. IR3G also significantly abrogated MPP+-induced mitochondrial fission. ConclusionIR3G inhibits MPP+-induced mitochondrial injury to abrogate apoptosis in PC-12 cells.

参考文献/References:

[1]BLESA J, PRZEDBORSKI S. Parkinson’s disease: animal models and dopaminergic cell vulnerability[J]. Front Neuroanat, 2014,8:155. DOI:10.3389/fnana.2014.00155.
[2]LOTHARIUS J, BRUNDIN P. Pathogenesis of Parkinson’s disease: dopamine,vesicles and alphasynuclein[J]. Nat Rev Neurosci, 2002,3(12):932-942. DOI:10.1038/nrn983.
[3]LEWIS P A,COOKSON M R. Gene expression in the Parkinson’s disease brain[J].Brain Res Bull, 2012,88(4):302-312. DOI:10.1016/j.brainresbull.2011.11.016.
[4]杨卫东.返朴归真回归自然——21世纪民族医药的展望[J].中国民族医药杂志,2008(2):74-75. DOI:10.16041/j.cnki.cn151175.2008.02.020.
YANG W D. Returning to the basics and returning to naturethe prospect of national medicine in the 21st century[J]. J Med Pharm Chin Minorities,2008(2):74-75. DOI:10.16041/j.cnki.cn151175.2008.02.020.
[5]阿丽塔,刘晓婷,王敏.抗帕金森病新药的研发进展[J].中国药事,2016,26(6):629-633.DOI:10.16153/j.10027777.2012.06.030.
A L T,LIU X T,WANG M.Advances of the research and development of new antiParkinson’s disease drugs[J]. Chin Pharm Affair, 2016,26(6):629-633. DOI:10.16153/j.10027777.2012.06.030.
[6]韦春英,韩敏.帕金森病治疗进展[J].内科,2014,9(3):360-362. DOI:10.16121/j.cnki.cn451347/r.2014.03.049.
WEI C Y, HAN M.Advances of the treatment of Parkinson’s disease[J]. Inter Med ,2014,9(3):360-362.DOI:10.16121/j.cnki.cn451347/r.2014.03.049.
[7]WERSINGER C,SIDHU A.An inflammatory pathomechanism for Parkinson’s disease[J]. Curr Med Chem,2006,13(5):591-602. DOI:10.2174/092986706776055760.
[8]熊珮,陈忻,张楠,等.帕金森病病理机制及中药防治帕金森病实验研究进展[J].中国中药杂志, 2012, 37(5): 686-691.
XIONG P,CHEN X,ZHANG N,et al.Advance in studies on pathological mechanism of Parkinson’s disease and traditional Chinese medicine experiments in prevention and treatment of Parkinson’s disease[J]. Chin J Chin Mater Med, 2012,37(5):686-691.
[9]SUBRAMANIAM S R, CHESSELET M F. Mitochondrial dysfunction and oxidative stress in Parkinson’s disease[J].Prog Neurobiol,2013:17-32. DOI:10.1016/j.pneurobio.2013.04.004.
[10]唐涌,肖成华.细胞凋亡在帕金森病发病中的作用[J].徐州医学学报,2004,24(1):87-90.DOI:10.3969/j.issn.10002065.2004.01.039.
TANG Y, XIAO C H.Role of apoptosis in the pathogenesis of Parkinson’s disease[J].Acta Acad Med Xuzhou,2004,24(1):87-90. DOI:10.3969/j.issn.10002065.2004.01.039.
[11]RAVISHANKAR D, RAJORA A K, GRECO F,et al. Flavonoids as prospective compounds for anticancer therapy[J]. Int J Biochem Cell Biol, 2013, 45(12):2821-2831. DOI:10.1016/j.biocel.2013.10.004.
[12]XIA X H, ZHANG Y, XI Y B,et al. Advances in studies on chemical constituents and bioactivities actions of ginkgo biloba L[J]. Chin J Exp Tradit Med Formulae, 2009, 15:100-104.
[13]IGARASHI K,MIKAMI T,TAKAHASHI Y,et al. Comparison of the preventive activity of isorhamnetin glycosides from atsumikabu (red turnip, brassica campestris l.) leaves on carbon tetrachlorideinduced liver injury in mice[J]. Biosci Biotechnol Biochem, 2008,72(3):856-860. DOI:10.1271/bbb.70558.
[14]DEVI V G,ROOBAN B N,SASIKALA V, et al. Isorhamnetin3glucoside alleviates oxidative stress and opacification in selenite cataract in vitro[J]. Toxicol In Vitro, 2010, 24(6): 1662-1669. DOI:10.1016/j.tiv.2010.05.021.
[15]卢芳,刘树民,杨婷婷.帕金森病的最新国内外研究进展[J].中国老年学杂志,2009,29(9):1171-1174.DOI: 10.3969/j.issn.10059202.2009.09.062.
LU F, LIU S M, YANG T T.Latest research progress at home and abroad of Parkinson’s disease[J]. Chin J Gerontol, 2009,29(9):1171-1174.DOI:10.3969/j.issn.10059202.2009.09.062.
[16]HANCOCK D B, MARTIN E R, MAYHEW G M, et al. Pesticide exposure and risk of Parkinson’s disease:a familybased casecontrol study[J]. BMC Neurol, 2008,8:6. DOI:10.1186/1471237786.
[17]李婷婷,梁迎春.帕金森病体外细胞模型[J].医学综述,2013,19(6):1003-1006.
LI T T,LIANG Y C. In vitro models of Parkinson disease[J]. Med Recapitulate,2013,19(6):1003-1006.
[18]TAMILSELVAM K, BRAIDY N, MANIVASAGAM T, et al. Neuroprotective effects of hesperidin, a plant flavanone, on rotenoneinduced oxidative stress and apoptosis in a cellular model for Parkinson’s disease[J]. Oxid Med Cell Longev, 2013,2013:102741. DOI:10.1155/2013/102741.
[19]李生华,黄伟华.BclxL在恶性肿瘤中应用的研究进展[J].医学综述,2007,13(7):501-503.
LI S H,HUANG W H.BclxL and malignant tumor in human[J]. Med Recapitulate,2007,13(7):501-503.

相似文献/References:

[1]刘天蔚,谢俊霞.TH和GDNF双基因表达载体的构建及其在MES23.5细胞中的表达[J].第三军医大学学报,2008,30(01):53.
 LIU Tian-wei,XIE Jun-xia.Construction of TH-GDNF vector and its expression in a dopaminergic cell line MES23.5[J].J Third Mil Med Univ,2008,30(23):53.
[2]陈平,汪世龙,陈震,等.MnTDM阻断百草枯诱导的N27细胞生长抑制的作用[J].第三军医大学学报,2007,29(24):2343.
 CHEN Ping,WANG Shi-long,CHEN Zhen,et al.Protective effects of SOD mimetic on N27 cell injury induced by Paraquat[J].J Third Mil Med Univ,2007,29(23):2343.
[3]梁亚杰,李淑蓉,苏炳银.MPTP致小鼠黑质致密部多巴胺能神经元损伤及定量研究[J].第三军医大学学报,2006,28(05):454.
[4]赵黔鲁,柴锡庆.鱼藤酮致PC12细胞线粒体功能及超微结构的影响[J].第三军医大学学报,2005,27(07):632.
[5]郭咏萍,蒋晓江,周红杰,等.62例帕金森病伴排尿困难患者临床处理[J].第三军医大学学报,2008,30(14):1385.
 GUO Yong-ping,JIANG Xiao-jiang,ZHOU Hong-jie,et al.Management for Parkinson’s disease patients with urine voiding dysfunction: report of 62 cases[J].J Third Mil Med Univ,2008,30(23):1385.
[6]王法祥,彭国光,王加才,等.优化hα-syn基因疫苗预防注射对MPTP急性帕金森病小鼠的神经保护作用[J].第三军医大学学报,2009,31(18):1761.
 WANG Fa-xiang,PENG Guo-guang,WANG Jia-cai,et al.Preventative immunization of optimized human α-synuclein DNA vaccine protects acute mouse with MPTP-induced Parkinson’s disease[J].J Third Mil Med Univ,2009,31(23):1761.
[7]张静丽,李江超,黎冰林,等.阿尔茨海默病和帕金森病患者血清代谢组学研究[J].第三军医大学学报,2016,38(05):522.
 Zhang Jingli,Li Jiangchao,Li Binglin,et al.Serum metabolic differences between the patients with Alzheimer’s and Parkinson’s diseases[J].J Third Mil Med Univ,2016,38(23):522.
[8]荣晶晶,李七渝,谭立文,等.基于可视人的帕金森病手术靶点核团定位初步研究[J].第三军医大学学报,2012,34(06):500.
 Rong Jingjing,Li Qiyu,Tan Liwen,et al.A preliminary study on operation target localization of Parkinson’s disease based on Chinese visible human[J].J Third Mil Med Univ,2012,34(23):500.
[9]李凤,陈明,马勋泰,等.甲磺酸雷沙吉兰治疗原发性帕金森病的随机、双盲、安慰剂对照临床试验[J].第三军医大学学报,2014,36(07):696.
 Li Feng,Chen Ming,Ma Xuntai,et al.Efficacy and safety of rasagiline mesylate in treatment of idiopathic Parkinson’s disease with motor fluctuations: a randomized, double-blind, parallel-controlled, single-center trial[J].J Third Mil Med Univ,2014,36(23):696.
[10]杨辉,蔡文琴,张可成,等.胎脑黑质脑内移植后帕金森病大鼠纹状体内THmRNA含量的研究[J].第三军医大学学报,1996,18(01):0.[doi:10.16016/j.1000-5404.1996.01.008 ]
 Yang Hui,CaiWenqin,Zhang Kecheng.[J].J Third Mil Med Univ,1996,18(23):0.[doi:10.16016/j.1000-5404.1996.01.008 ]

更新日期/Last Update: 2018-12-19