洛伐他汀对抗AβOs引起的SH-SY5Y细胞毒性作用Antagonism of Lovastatin on Cytotoxicity in SH-SY5Y Cells Induced by β-Amyloid Peptide Oligomers
谭龙春,吴昌学,赵亮,董阳婷,刘仙红,官志忠
TAN Longchun,WU Changxue,ZHAO Liang,DONG Yangting,LIU Xianhong,GUAN Zhizhong
摘要(Abstract):
目的:观察洛伐他汀对抗Aβ寡聚体(AβOs)引起的SH-SY5Y细胞毒性作用。方法:生长至80%~90%并用无血清培养基培养12 h的SH-SY5Y细胞分为对照组、洛伐他汀处理组(0.1μmol/L洛伐他汀处理24 h)、AβOs处理组(0.5μmol/L AβOs处理48 h)和洛伐他汀加AβOs处理组(0.1μmol/L洛伐他汀处理24 h,再加入0.5μmol/L AβOs继续处理48 h),采用CCK-8法检测各组细胞活性,使用相应的试剂盒检测细胞超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GSH-Px)活性、丙二醛(MDA)含量。结果:0.5μmol/L AβOs处理SHSY5Y细胞48 h后,与对照组相比,SH-SY5Y细胞活性、SOD及GSH-Px活性显著降低,MDA含量明显增加(P<0.05);在0.5μmol/L AβOs处理SH-SY5Y细胞前,预先用0.1μmol/L洛伐他汀处理细胞24 h,可减弱AβOs引起的细胞活性、SOD和GSH-Px活性及MDA含量的改变(P<0.05)。结论:洛伐他汀可对抗AβOs引起的SHSY5Y细胞毒性作用,其保护机制可能与抑制氧化应激有关。
Objective: To investigate the effect of lovastatin on cytotoxicity in SH-SY5 Y cells induced by β-Amyloid peptide oligomers( AβOs). Methods: When SH-SY5 Y cells were grown to 80% ~90% and cultured in serum-free medium for 12 h,they were divided into control group,lovastatin group( 0. 1 μmol/L lovastatin for 24 h),AβOs group( 0. 5 μmol/L βOs for 48 h) and lovastatin +AβOs group( 0. 1 μmol/L lovastatin treated with for 24 h,and then treated with 0. 5 μmol/L AβOs for 48 h). The cell viability was measured by CCK-8 assay,superoxide dismutase( SOD) and glutathione peroxidase( GSH-PX) activities and malondialdehyde( MDA) content were measured by appropriate biochemical methods. Results: As compared with control group,the cell viability,SOD and GSH-PX activities were significant decreased,while MDA content was significantly increased after SHSY5 Y cells treated with 0. 5 μmol/L AβOs for 48 h( P < 0. 05). When SH-SY5 Y cells were treatedwith 0. 1 μmol/L lovastatin for 24 h before treatments of AβOs,these cytotoxicity resulted by AβOs indicated as cell viability,SOD and GSH-PX activity and MDA content were all significantly attenuated( P < 0. 05). Conclusions: Lovastatin could antagonize the cytotoxicity in SH-SY5 Y cells caused by AβOs,and the mechanism might relate to the inhibition of oxidative stress.
关键词(KeyWords):
阿尔茨海默病;洛伐他汀;Aβ寡聚体;细胞毒性;氧化应激;SH-SY5Y细胞
Alzheimer disease;lovastatin;β-amyloid peptide oligomers;cytotoxicity;oxidative stress;SH-SY5Y cells
基金项目(Foundation): 国家自然科学基金(81260173);; 教育部“长江学者和创新团队发展计划资助”(IRT13058);; 贵州省科技计划[黔科合重大专项字(2014)6008号];; 贵州省创新计划项目[黔教合协同创新中心(2014)06]
作者(Author):
谭龙春,吴昌学,赵亮,董阳婷,刘仙红,官志忠
TAN Longchun,WU Changxue,ZHAO Liang,DONG Yangting,LIU Xianhong,GUAN Zhizhong
DOI: 10.19367/j.cnki.1000-2707.2017.06.007
参考文献(References):
- [1]Reitz C,Brayne C,Mayeux R.Epidemiology of Alzheimer disease[J].Nature Reviews Neurology,2011(8):137-152.
- [2]YG,JD,CB,et al.Aβ42 oligomers modulateβ-secretase through an XBP-1s-dependent pathway involving HRD1[J].Scientific Reports,2016(6):186-194.
- [3]Association AS.2015 Alzheimer's disease facts and figures[J].Alzheimers&Dementia the Journal of the Alzheimers Association,2015(3):332-384.
- [4]Vinters HV.Emerging concepts in Alzheimer's disease[J].Pathology:Mechanisms of Disease,2015(10):291-319.
- [5]Gandhi S,Abramov AY.Mechanism of oxidative stress in neurodegeneration[J].Oxidative Medicine&Cellular Longevity,2012(3):428010-428030.
- [6]Ankarcrona M,Mangialasche F,Winblad B.Rethinking Alzheimer's disease therapy:are mitochondria the key[J].Journal of Alzheimers Disease Jad,2010(suppl 2):579-590.
- [7]Kellick KA,Bottorff M,Toth PP.A clinician's guide to statin drug-drug interactions[J].Journal of Clinical Lipidology,2014(3):30-46.
- [8]Carlsson CM,Xu G,Wen Z,et al.Effects of atorvastatin on cerebral blood flow in middle-aged adults at risk for Alzheimer's disease:a pilot study[J].Current Alzheimer Research,2012(8):990-997.
- [9]Ai H,Araki W,Oda A,et al.Statins reduce amyloidβ-peptide production by modulating amyloid precursor protein maturation and phosphorylation through a cholesterolindependent mechanism in cultured neurons[J].Neurochemical Research,2013(3):589-600.
- [10]Neuroscience N.The toxic Aβoligomer and Alzheimer's disease:an emperor in need of clothes[J].Nature Neuroscience,2012(3):349-357.
- [11]Nichols MR,Colvin BA,Hood EA,et al.Biophysical comparison of soluble Amyloid-β(1-42)protofibrils,oligomers,and protofilaments[J].Biochemistry,2015(13):2193-2204.
- [12]Shitara Y,Sugiyama Y.Pharmacokinetic and pharmacodynamic alterations of 3-hydroxy-3-methylglutaryl coenzyme A(HMG-Co A)reductase inhibitors:drug-drug interactions and interindividual differences in transporter and metabolic enzyme functions[J].Pharmacology&Therapeutics,2006(1):71-105.
- [13]Kandiah N,Feldman HH.Therapeutic potential of statins in Alzheimer's disease[J].Journal of the Neurological Sciences,2009(1-2):230-234.
- [14]Shepardson NE,Shankar GM,Selkoe DJ.Cholesterol level and statin use in Alzheimer disease:I.Review of epidemiological and preclinical studies[J].Archives of Neurology,2011(10):1239-1244.
- [15]KR,MS,BF,et al.Statins and cognitive function:a systematic review[J].Annals of Internal Medicine,2013(10):688-697.
- [16]Barone E,Cenini G,Di DF,et al.Long-term high-dose atorvastatin decreases brain oxidative and nitrosative stress in a preclinical model of Alzheimer disease:a novel mechanism of action[J].Pharmacological Research,2011(3):172-180.
- [17]Butterfield DA,Barone E,Mancuso C.Cholesterol-independent neuroprotective and neurotoxic activites of statins:prespectives for statin use in alzheimer disease and other age-related neurodegenerative disorders[J].Pharmacological Research,2011(3):180-186.
- [18]Ha KG,Kim JE,Jeong RS,et al.The role of oxidative stress in neurodegenerative diseases[M].Springer New York,2015:151-167.
- [19]Zhao Y,Zhao B.Oxidative stress and the pathogenesis o alzheimer's disease[J].Oxidative Medicine&Cellular Longevity,2013(6):316523-316540.
- [20]Picone P,Nuzzo D,Caruana L,et al.Mitochondria dysfunction:different routes to alzheimer's disease therapy[J].Oxidative Medicine&Cellular Longevity,2014(2):780179-780192.
- [21]赵虹,骆庆和,殷明,等.氧化应激与阿尔茨海默病[J].中国老年学,2013(16):4090-4093.
- [22]Larson ME,LesnéSE.Soluble Aβoligomer production and toxicity[J].Journal of Neurochemistry,2012:125-139.
- [23]Selkoe DJ.Soluble oligomers of the amyloidβ-protein impair synaptic plasticity and behavior[J].Behavioura Brain Research,2008(1):106-113.
- [24]Yankner BA,Lu T.Amyloidβ-protein toxicity and the pathogenesis of alzheimer disease[J].Journal of Biological Chemistry,2008(8):4755-4759.
- [25]Mucke L,Selkoe DJ.Neurotoxicity of amyloidβ-protein:synaptic and network dysfunction[J].Cold Spring Harbor Perspectives in Medicine,2012(7):a6338.
- [26]黄海,陈丽君,陈立艺,等.Aβ1-42寡聚体对大鼠认知功能的影响和神经毒性分析[J].解剖学杂志,2015(6):698-701.
文章评论(Comment):
|
||||||||||||||||||
|
- 阿尔茨海默病
- 洛伐他汀
- Aβ寡聚体
- 细胞毒性
- 氧化应激
- SH-SY5Y细胞
Alzheimer disease - lovastatin
- β-amyloid peptide oligomers
- cytotoxicity
- oxidative stress
- SH-SY5Y cells