摘要
阿尔茨海默病(Alzheimer’s disease,AD)是一种与衰老相关的神经退行性疾病,其中β-淀粉样蛋白(β-amyloid,Aβ)诱导的细胞毒性被认为是其发病的主要原因。本文以Aβ转基因秀丽隐杆线虫CL4176为模型,研究了重组荞麦谷氧还蛋白(recombinant buckwheat glutaredoxin,rbGrx)对Aβ诱导的毒性和氧化应激的影响。结果显示,4μmol/L rbGrx可以延长CL4176线虫平均寿命达20%左右,并增加衰老虫体运动能力约43.6%,延迟产卵高峰期1 d,同时可以有效延缓Aβ毒性诱导的瘫痪表型。进一步研究发现,在正常条件和Aβ诱导毒性时,rbGrx均能降低CL4176线虫体内活性氧(reactive oxygen species,ROS)水平,并上调SOD活性和GSH含量。另外,rbGrx下调AβmRNA水平44.1%,减少Aβ沉积量,并且明显上调热激因子1 hsf-1(2.01倍)和hsp-16.2(2.65倍)mRNA表达水平。这表明,rbGrx通过降低CL4176线虫体内的ROS水平和上调热激蛋白质的转录表达水平,降低CL4176秀丽隐杆线虫中Aβ诱导的毒性。结果提示,rbGrx可能具有预防AD的潜力。
Alzheimer＇s disease（AD） is an age-related neurodegenerative disease,of which β-amyloid（Aβ） induced toxicity was suggested as a main cause. We investigated the effects of recombinant buckwheat glutaredoxin（rbGrx） on Aβ-induced toxicity and oxidative stress in a transgenic AD Caenorhabditis elegans（C. elegans） model. Our study showed that rbGrx not only increased the lifespan and locomotion by 20% and 43. 6% respectively,but also delayed spawning peak for 1 day and Aβ-induced paralysis in the transgenic model as compared with control group. Further study indicated that rbGrx upregulated the SOD activity for 2. 5-fold and the GSH content for 2. 19-fold,leading to a low intracellular level of reactive oxygen species（ROS） in AD transgenic C. elegans in both normal and Aβ-induced paralysis condition. Moreover,rbGrx down-regulated Aβ mRNA level by 44. 1% and decreased the amount of Aβ deposits. rbGrx also significantly increased the mRNA expression levels of hsf-1 and hsp-16. 2 by 2. 01-fold and 2. 65-fold,respectively. Taken together,these results suggested that rbGrx reduces Aβ-induced toxicity in transgenic C. elegans by decreasing ROS levels and upregulating the expression of heat shock proteins,implying that rbGrx may have the potential to prevent AD.
作者
李芳
崔晓东
马晓丽
李娇
王转花
LI Fang;CUI Xiao-Dong;MA Xiao-Li;LI Jiao;WANG Zhuan-Hua(Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education,Institute of Biotechnology Shanxi University,Taiyuan 030006,China;College of Life Sciences,Shanxi University,Taiyuan 030006,China;Shaaxi Academy of Medical Sciences,Shanxi Dayi Hospital,Taiyuan 030032,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2018年第8期844-853,共10页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金项目(No.31600631,No.31300653)
山西省青年科技研究基金(No.201601D202102)资助
