Transcriptomic analysis:the protection of over-expression thioredoxin reductase 1 in Parkinson’s disease  

作　　者：Zihua Liu Qiang Ye Ying Jiang 

机构地区：[1]Department of Blood Transfusion Service,the Second Affiliated Hospital of Lanzhou University,Lanzhou 730030,Gansu Province,China [2]Department of Anatomy and Histology,School of Basic Medical Sciences,Lanzhou University,Lanzhou,China [3]Intensive Care Center of Gynecology and Obstetrics,Gansu Provincial Maternity and Childcare Hospital,Lanzhou 730050,Gansu,China

出　　处：《Chinese Neurosurgical Journal》2023年第3期199-211,共13页中华神经外科杂志（英文）

基　　金：supported by the Cuiying Science and technology Innovation Project(CY2021-MS-B07);Cuiying studentsp scientific research and cultivation program(CYXZ2020-34);Natural Science Foundation of Gansu Province(22JR5RA987)

摘　　要：Background Parkinson’s disease(PD)is the second most common neurodegenerative disease.The pathologic characteristic feature is the loss of dopaminergic neurons in the substantia nigra(SN).However,the biochemical mechanisms are unclear.A large number of studies have shown that oxidative damage is the primary cause of PD.Hence,antioxidants could become a suitable option to treat PD.The thioredoxin(Trx)system represents a useful,potentially disease-relevant oxidation-reduction system.Thioredoxin reductase 1(TR1)is a significant component of the Trx system.Methods The overexpression lentivirus(LV)or LV-TR1 in the TR1-A53T model of PD by the stereotactic brain,and successful overexpression of LV or LV-TR1 in the MPP^(+)-induced cellular model by LV or LV-TR1 transfection.Results We confirmed that interleukin-7 mRNA levels increased in MPP^(+)compared to that in the control and MPP^(+)-TR1 groups using quantitative polymerase chain reaction.Theγ-H_(2)AX level was increased in the Tg-A53T group compared to that in the TR1-A53T group by western blotting.The expression of Na^(+)-K^(+)-ATP was decreased in the MPP^(+)group compared to that in the control and MPP^(+)-TR1 groups by high content screening.Tg-A53T(the C57BL/6 mice transferred with mutant human a-syn);TR1-A53T(A53T mice which were injected TR1-LV 2µl in SNc on two sides with minipump).The mice were fed for 10 months.control(the N2a cells cultivated with DMEM);MPP^(+)(the N2a cells dealt with MPP^(+)(1 mM)48 h),MPP^(+)-LV(the N2a cells over-expressed LV for 24 h then dealt with MPP^(+)(1 mM)48 h).MPP^(+)-TR1(the N2a cell over-expressed TR1-LV for 24 h then dealt with MPP^(+)(1 mM)48 h).From the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis,we confirmed that the overexpression of TR1 in SN pars compacta cells decreased oxidative stress,apoptosis,DNA damage,and inflammatory response and increased NADPH,Na^(+)-K^(+)-ATP,and immune response in this PD model.Conclusions Our study shows that overexpressed TR1 can be developed as a neuroprotective agent for

关 键 词：Parkinson’s disease Thioredoxin reductase 1 Na^(+)-K^(+)-ATP TLR2 CD14 

分 类 号：R742.5[医药卫生—神经病学与精神病学]