Overexpression of Myocardin-related transcription factor-A attenuated middle cerebral artery occlusion/reperfusion-induced apoptosis via the Mcl-1/Cyt C/cleaved caspase 3 pathway  

作　　者：Zhi-Jun Yu Jing Du Wei Zhang Shu-Qi Zhao Wei Dong Shi-Qiang Xu Ling Hu Zhen-Li Min Qiong Yuan Chunxiang Zhang Xia-Min Hu 

机构地区：[1]New Drugs Innovation Institute Wuhan University of Science and Technology Wuhan 430065,P.R.China [2]Shanghai University of Medicine and Health Sciences Shanghai 200000,P.R.China [3]Department of Rehabilitation Medicine China Resources&WISCO General Hospital Wuhan 430080,P.R.China [4]Department of Biomedical Engineering School of Medicine and School of Engineering The University of Alabama at Birmingham Birmingham,AL 35294,USA [5]Department of Pharmacy,Wuhan Asia Heart Hospital Wuhan,Hubei Province 430000,P.R.China [6]Hubie Provincial Key Laboratory of Occupational Hazard Identication and Control Wuhan University of Science and Technology Wuhan 430065,P.R.China

出　　处：《Journal of Innovative Optical Health Sciences》2019年第6期199-209,共11页创新光学健康科学杂志（英文）

基　　金：supported by the National Nature Science Foundation of China(Nos.31171327 and 81770377);the Nature Science Foundation of Hubei Province(No.2017CFB448).

摘　　要：To investigate the effect of Myocardin related transcription factor A(MRTF-A)on apoptosis induced by ischemic/reperfusion(I/R),middle cerebral artery occlusion/reperfusion(MCAO/R)in rats were applied to mimic I/R.The neurological deficit score,cerebral infarct size,cortical neuron apoptosis and cleaved caspase 3 level were evaluated to determine the effect and the level of apoptosis by TTC straining,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)straining,Western blot and immunofuorescence staining.The myeloid cell leukemia-1(Mcl-1)expression,release of cytochrome C(Cyt C)and its colocalization with apoptotic pro-tease activating factor-1(Apaf-1)were analyzed by quantitative real-time PCR(qRT-PCR),Western blot,and immunofuorescence staining.The results showed that MRTF-A over-expression could decrease the neurological deficit score and reduce cerebral infarct size(P<0.01 versus Sham).In the MRTF-A-I/R group,TUNEL-positive cells and apoptosis ratio(%)(51.61±6.17%)were significantly decreased compared to the Neg-I/R group(76.45±8.77%)at 24 h reperfusion.Meanwhile,the cleaved caspase 3 expression revealed a similar trend while the expression of Mcl-1 was the opposite.Moreover,MRTF-A overexpression significantly enhanced Mcl-1 fAuorescence intensity,which up-regulated the mRNA and protein level(P<0.05or P<0.01 versus Neg-I/R).Furthermore,MRTF-A overexpression markedly inhibited the release of Cyt C,and decreased the colocalization with Apaf-1 in the cytoplasm(P<0.05 or P<0.01.versus Neg-I/R).All the data indicated that MRTF-A overexpression could improve the neu-rological function against cerebral I/R-induced apoptosis since underlying mechanism might be involved in the Mc-1/Cyt C/cleaved caspase 3 signaling pathway.

关 键 词：Stroke animal model immunofuorescence staining laser scanning confocal microscope 

分 类 号：R542.2[医药卫生—心血管疾病]