[1]张红梅,张雄,李昱.姜黄素对阿尔采末病中APP淀粉样酶切途径的调控作用[J].中国药理学通报,2009,(03):0.
 ZHANG Hong mei,ZHANG Xiong,LI Yu.pathaway of APP in Alzheimers disease[J].Chinese Pharmacological Bulletin,2009,(03):0.
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姜黄素对阿尔采末病中APP淀粉样酶切途径的调控作用()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2009年03期
页码:
0
栏目:
论著
出版日期:
2009-03-25

文章信息/Info

Title:
pathaway of APP in Alzheimers disease
作者:
张红梅张雄李昱
重庆医科大学病理学教研室,重庆400016
Author(s):
ZHANG Hongmei ZHANG Xiong LI Yu
Dept of Pathology ,Chongqing Medical University, Chongqing400016, China
关键词:
阿尔采末病姜黄素APPBACE1
Keywords:
Alzheimers disease curcumin APP BACE1
分类号:
R 28271;R 3292;R 34222
文献标志码:
A
摘要:
目的研究姜黄素作用于阿尔采末病中APP淀粉样酶切途径的环节,探讨其抑制Aβ产生的作用机制。方法体外培养SHSY5Y细胞,以LipofectaminTM2000脂质体介导瞬时共转染pBACE1mychis和pAPPswe两种质粒,姜黄素(0、125、50、20 μmol·L-1)处理转染后的SHSY5Y细胞 24 h,以及5 μmol·L-1姜黄素按时间梯度(0、12、24、48 h)分别处理转染后的SHSY5Y细胞,通过RTPCR检测APP和BACE1 mRNA水平,Western blot检测BACE1和C99蛋白表达情况,ELISA检测Aβ40/42水平。结果经姜黄素处理后APP和BACE1 mRNA表达水平都有明显减弱,呈浓度-时间依赖性(P<005);BACE1和C99蛋白表达也有不同程度的下调,呈浓度-时间依赖性(P<005);Aβ40/42表达水平明显降低,呈浓度-时间依赖性(P<005)。结论姜黄素能够抑制阿尔采末病相关基因APP mRNA表达;抑制APP的限速酶BACE1 mRNA和蛋白表达;并抑制APP分解产物C99蛋白表达,都呈浓度-时间依赖性(P<005)。此外,姜黄素可以明显抑制APP的分解产物Aβ40/42的产生。
Abstract:
AimTo investigate the effects of Curcumin on the APP processing in the amyloidogenic pathway in vitro and explore its mechanisms on Aβ generation inhibition.MethodsPlasmids APPswe and BACE1mychis were transiently cotransfected in SHSY5Y cell by LipofectaminTM2000. The cell line then treated with Curcumin at 0, 125, 5, 20 μmol·L-1 for 24 h, or with Curcumin at 5 μmol·L-1 for 0, 12, 24 and 48 h for the time course assay. RTPCR were performed to measure the endogenous levels of APP and BACE1 mRNA. Western blot were used to detect the protein expression of BACE1 and C99, the major βsecretase cleavage product. The concentration of Aβ40/42 was detected by βamyloid 1 40 or 42 Colorimetric ELISA.ResultsRTPCR results showed that the mRNA levels of APP and BACE1 were decreased obviously in a doseand timedependent manner after treated with Curcumin in SHSY5Y (P<005). Western Blotting results showed that the expression of BACE1 and C99 protein were all decreased in a doseand timedependent manner (P<005). ELISA results showed that the generation of Aβ40/42 reduced significantly, also in a doseand timedependent manner (P<005).ConclusionOur finding demonstrated that Curcumin could inhibit the expression of the APP at mRNA; the expression of the BACE1 at mRNA and protein levels, furthermore it could inhibit the generation of Aβ40/42,and those changes were dosetime dependent (P<005).Those factors are key components in APP amyloidogenic pathway.

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备注/Memo

备注/Memo:
收稿日期:2008-11-26,修回日期:2008-12-30基金项目:国家自然科学基金资助项目(No 30600196);重庆市自然科学基金资助项目(No CSTC,2006BB5042);2007年教育部留学回国人员科研启动基金(No 教外司留[2007]1108号)。作者简介:张红梅(1980-),女,硕士生,研究方向:药物治疗阿尔采末病,Email:zhmje@126.com;张雄(1978-),男,硕士生,研究方向:药物治疗阿尔采末病,Email :zhangxiong_0@yahoo.com.cn;李昱(1973-),女,博士,教授,硕士生导师,通讯作者,研究方向:药物治疗阿尔采末病,Email:liyu100@163.com张红梅、张雄同为第一作者。
更新日期/Last Update: 2009-03-25