摘要
目的研究洛伐他汀对淀粉样前体蛋白β位点裂解酶(β-site APP cleaving enzyme,BACE1)表达和活性的影响。方法予洛伐他汀对SH-SY5Y细胞系进行处理;通过噻唑蓝比色(MTT)法观察其对细胞活力的影响;采用酶法测定胆固醇含量,采用荧光光度法测定BACE1活性,采用WesternBlot方法检测BACE1蛋白的表达量。结果与对照组相比,5μmol/L洛伐他汀组作用24h后细胞胆固醇水平下降33.0%(胆固醇与总蛋白含量的比值:3.33vs.4.97;F=5.13,P=0.020),同时BACE1活性下降13.8%(343.14vs.398.22;F=3.773,P=0.035);5μmol/L洛伐他汀组作用48h后细胞胆固醇水平下降49.2%(胆固醇与总蛋白含量的比值:2.65vs.5.22;F=12.239,P=0.001),同时BACE1活性下降38.0%(274.75vs.443.14;F=13.610,P<0.01);洛伐他汀组BACE1蛋白表达量与对照组相比无统计学差异(P>0.05)。结论洛伐他汀不影响BACE1蛋白的表达,但可以抑制BACE1蛋白的活性,同时伴细胞胆固醇水平降低,这为阿尔茨海默病(Alzheimersdisease,AD)的防治提供了新的思路。
Objective To study the effect of lovastatin on the expression and activity of β-site APP cleaving enzyme (BACE1).Methods The SH-SY5Y cells were treated by lovastatin.Cell viability was assessed by MTT assay,and the levels of cholesterol were assayed spectrophotometrically,and the activity of BACE1 was detected by fluorometric assay,and the expression level of BACE1 was detected by Western Blot.Results Compared with the control group,the cholesterol levels were decreased by 33.0% (3.33 vs.4.97;F=5.13,P=0.020) and the activity of BACE1 was reduced by 13.8% (343.14 vs.398.22;F=3.773,P=0.035) after 24h treatment of 5μmol/L lovastatin;the cholesterol levels were decreased by 49.2% (2.65 vs.5.22;F=12.239,P=0.001) and the activity of BACE1 was reduced by 38.0% (274.75 vs.443.14;F=13.610,P0.01).Treatment with 5μmol/L lovastatin,for 48 h did affect the expression level of BACE1.Conclusions Lovastatin do not affect the expression level of BACE1,but may inhibit its activity and decrease the cholesterol level,thus providing a new approach to prevent or treat Alzheimer's disease (AD).
出处
《中国神经精神疾病杂志》
CAS
CSCD
北大核心
2010年第2期80-83,共4页
Chinese Journal of Nervous and Mental Diseases
基金
国家973基金资助项目(编号:2006CB500700)
北京自然科学基金重点资助项目(编号:7071004)