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

Chinese Neurosurgical Journal 2023年第3期9卷 199-211页

作者： Zihua Liu Qiang Ye Ying Jiang Department of Blood Transfusion Service the Second Affiliated Hospital of Lanzhou UniversityLanzhou 730030Gansu ProvinceChina Department of Anatomy and Histology School of Basic Medical SciencesLanzhou UniversityLanzhouChina Intensive Care Center of Gynecology and Obstetrics Gansu Provincial Maternity and Childcare HospitalLanzhou 730050GansuChina

Background Parkinson’s disease(PD)is the second most common neurodegenerative *** 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 ***,antioxidants could become a suitable option to treat *** thioredoxin(Trx)system represents a useful,potentially disease-relevant oxidation-reduction *** reductase 1(TR1)is a significant component of the Trx *** 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 *** We confirmed that interleukin-7 mRNA levels increased in MPP^(+)compared to that in the control and MPP^(+)-TR1 groups using quantitative polymerase chain ***γ-H_(2)AX level was increased in the Tg-A53T group compared to that in the TR1-A53T group by western *** expression of Na^(+)-K^(+)-ATP was decreased in the MPP^(+)group compared to that in the control and MPP^(+)-TR1 groups by high content ***-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 ***(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 *** Our study shows that overexpressed TR1 can

关键词： Parkinson’s disease thioredoxin reductase 1 Na^(+)-K^(+)-ATP TLR2 CD14

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Broken electron transfer pathway in enzyme:Gold clusters inhibiting TrxR1/Trx via cell studies and theory simulations

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Chinese Chemical Letters 2022年第7期33卷 3488-3491页

作者： Wenchao Niu Zhongying Du Chunyu Zhang Deting Xu Jiaojiao Li Minghui Sun Liyuan Wu Haodong Yao Lina Zhao Xueyun Gao Department of Chemistry and Biology Beijing University of TechnologyBeijing 100124China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Beijing 100049China

thioredoxin reductase 1(TrxR1)is over activity in tumor cell to maintain their redox *** gold clusters have great potential in antitumor drug as they could well inhibit TrxR1,the molecular mechanism has not been disclosed *** this work,we revealed gold clusters can well inhibit the activity of TrxR1 in lung tumor cells and further disclosed the inhibition mechanism by using computational simulation *** firstly inferred the binding sites of gold in the hydrophobic cavities on *** simulation results show that the gold ion(released from Au cluster)interact with–SH of Cys189 in TrxR1,this greatly increase the distance between the C-terminal redox center of TrxR1 and the Trx redox center,thereby destroy the electron transfer pathway between *** electron transfer destroying mechanism is different from the previous hypothesis that gold binds to the Sec498 of TrxR1 which has never been proved by experimental and theory *** work provides a new understanding of the gold clusters to inhibit TrxR1 activity.

关键词： Enzyme inhibition Electron transfer thioredoxin reductase 1 Gold clusters Molecular dynamics Density functional theory

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