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| 1 | PrP mutants with different numbers of octarepeat sequences are more susceptible to the oxidative stress显示文摘One of the physiological functions of cellular prion protein(PrP C )is believed to work as a cellular resistance to oxidative stress,in which the octarepeats region within PrP plays an important role.However,the detailed mechanism is less clear.In this study,the expressing plasmids of wild-type PrP (PrP-PG5)and various PrP mutants containing 0(PrP-PG0),9(PrP-PG9)and 12(PrP-PG12)octarepeats were generated and PrP proteins were expressed both in E.coli and in mammalian cells.Protein aggregation and formation of carbonyl groups were clearly seen in the recombinant PrPs expressed from E.coli after treatment of H2O2.MTT and trypan blue staining assays revealed that the cells expressing the mutated PrPs within octarepeats are less viable than the cells expressing wild-type PrP.Statistically significant high levels of intracellular free radicals and low levels of glutathione peroxidase were observed in the cells transfected with plasmids containing deleted or inserted octarepeats.Remarkably more productions of carbonyl groups were detected in the cells expressing PrPs with deleted and inserted octarepeats after exposing to H2O2.Furthermore,cells expressing wild-type PrP showed stronger resistant activity to the challenge of H2O2 at certain extent than the mutated PrPs and mock. These data provided the evidences that the octarepeats number within PrP is critical for maintaining its activity of antioxidation.Loss of its protective function against oxidative stress may be one of the possible pathways for the mutated PrPs to involve in the pathogenesis of familial Creutzfeldt-Jacob diseases. | AN Run1 ,2,DONG ChenFang 2,LEI YanJun 1,2,HAN Lu 2,LI Ping 2,CHEN JianMing 2,WANG GuiRong 2, SHI Qi 2 ,GAO Chen 2 ,JIANG HuiYing 2 ,ZHOU Wei 2 ,HAN Jun 2 ,CHU YongLie 1 ,DONG XiaoPing 2 1School of Medicine,Xi’an JiaoTong University,Xi’an 710061,China 2State Key Laboratory for Infectious Disease Prevention and Control,National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention,YingXin Rd 100,Beijing 100052,China | 2008 | Science China(Life Sciences)2008，51，7： | 3 |
| 2 | Diagnostic and therapeutic advancements for aerobic vaginitis显示文摘 | Cha Han Wenjuan Wu Aiping Fan Yingmei Wang Huiying Zhang Zanjun Chu Chen Wang Fengxia Xue | 2015 | Archives of Gynecology and Obstetrics2015，，2： | 1 |
| 3 | Theoretical studies of interaction models of human acetylcholine esterase with different inhibitors显示文摘Alzheimer's disease(AD) is a progressive neurodegenerative disorder and one of the most common causes of dementia in the elderly.Acetylcholine esterase inhibitors(AChEI) are the main drugs used in the treatment of AD.In this work,docking studies have been performed in order to understand the interaction between a number of inhibitors(tacrine,rivastigmine,huperzine A,TV-3326(ladostigil),donepezil and anseculin) and acetylcholine esterase(AChE).The calculated binding affinities between inhibitors and AChE increase in the order tacrine | ZHENG QingChuan CHU HuiYing NIU RuiJuan SUN ChiaChung | 2009 | Science China Chemistry2009，52，11： | 0 |
| 4 | Fructose-1,6-bisphosphatase 1 dephosphorylates IκBα and suppresses colorectal tumorigenesis显示文摘Emerging evidence demonstrates that some metabolic enzymes that phosphorylate soluble metabolites can also phosphorylate a variety of protein substrates as protein kinases to regulate cell cycle,apoptosis and many other fundamental cellular processes.However,whether a metabolic enzyme dephosphorylates protein as a protein phosphatase remains unknown.Here we reveal the gluconeogenic enzyme fructose 1,6-biphosphatase 1(FBP1)that catalyzes the hydrolysis of fructose 1,6-bisphosphate(F-1,6-BP)to fructose 6-phosphate(F-6-P)as a protein phosphatase by performing a high-throughput screening of metabolic phosphatases with molecular docking followed by molecular dynamics(MD)simulations.Moreover,we identify IκBαas the substrate of FBP1-mediated dephosphorylation by performing phosphoproteomic analysis.Mechanistically,FBP1 directly interacts with and dephosphorylates the serine(S)32/36 of IκBαupon TNFαstimulation,thereby inhibiting NF-κB activation.MD simulations indicate that the catalytic mechanism of FBP1-mediated IκBαdephosphorylation is similar to F-1,6-BP dephosphorylation,except for higher energetic barriers for IκBαdephosphorylation.Functionally,FBP1-dependent NF-κB inactivation suppresses colorectal tumorigenesis by sensitizing tumor cells to inflammatory stresses and preventing the mobilization of myeloid-derived suppressor cells.Our finding reveals a previously unrecognized role of FBP1 as a protein phosphatase and establishes the critical role of FBP1-mediated IκBαdephosphorylation in colorectal tumorigenesis. | Wencheng Zhu Huiying Chu Yajuan Zhang Tianhang Luo Hua Yu Hongwen Zhu Ye Liu Hong Gao Yun Zhao Quanlin Li Xiongjun Wang Guohui Li Weiwei Yang | 2023 | Cell Research2023，33，3： | 0 |
| 5 | Cholesterol modulating the orientation of His17 in hepatitis C virus p7 (5a) viroporin--A molecular dynamic simulation study显示文摘Protein p7 of HCV is a 63 amino acid channel forming membrane protein essential for the progression of viral infection and the sensitivity of this channel to small-molecule inhibitors renders p7 a potential target for novel therapies against HCV infection. Previous biochemical experiments suggested that the His17 of p7 is a pore-lining residue and solvated-exposed to participate in channel gating. However, a recent NMR structural identi fication of the p7 hexamer in dodecylphosphocholine(DPC) micelles indicated that the His17 is embedded into the protein matrix. In this work, we performed molecular dynamic simulations to bridge the controversial observations. Our results illustrated that by incorporating the cholesterol into DOPC membranes to mimic an actual membrane-like composition,the orientation of His17 in the hexameric bundles spontaneously access to the central pore region,indicating a versatile property of the p7 viroporin conformation that could be voluntarily in fluenced by its surrounding environments. | Yuebin Zhang Xiangda Peng Hong Ren Huiying Chu Yan Li Guohui Li | 2018 | Chinese Chemical Letters2018，29，5： | 0 |
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