谷氧还蛋白rbGrx可延缓CL4176秀丽隐杆线虫中β淀粉样蛋白诱导的毒性  

Glutaredoxin Delays the Toxicity Induced by β-amyloid in AD Transgenic C. elegans

作　　者：李芳 崔晓东[1] 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)

机构地区：[1]化学生物学与分子工程教育部重点实验室,山西大学生物技术研究所,太原030006 [2]山西大学生命科学学院生物工程系,太原030006 [3]山西医学科学院山西大医院肿瘤内科,太原030032

出　　处：《中国生物化学与分子生物学报》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

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.

关 键 词：重组荞麦谷氧还蛋白 β-淀粉样蛋白 AD模型秀丽隐杆线虫 热激因子1 

分 类 号：Q599[生物学—生物化学]