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Biochemical reactions in metabolite-protein interaction

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Chinese Chemical Letters 2018年第5期29卷 645-647页

作者： Wen Wang Dinesh Singh Tekcham Min Yan Zhichao Wang Huan Qi Xiaolong Liu hai-long piao Scientific Research Center for Translational Medicine Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian 116023 China University of Chinese Academy of Sciences Beijing 100049 China CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian 116023 China

Active endogenous metabolites regulate the viability of cells. This process is controlled by a series ofinteractions between small metabolites and large proteins. Previously, several studies had reported thatmetabolite regulates the protein functions, such as diacylglycerol to protein kinase C, lactose regulationof the lac repressor, and HIF-1α stabilization by 2-hydroxyglutarate. However, decades old traditionalbiochemical methods are insufficient to systematically investigate the bio-molecular reactions for a high-throughput discovery. Here, we have reviewed an update on the recently developed chemical proteomicscalled activity-based protein profiling （ABPP）. ABPP is able to identify proteins interacted eithercovalently or non-covalently with metabolites significantly. Thus, ABPP will facilitate the characteriza-tion of specific metabolite regulating; proteins in human disease progression.

关键词： Post translational modification Activity-based protein profiling Metabolite-protein interaction Chemical probe Mass spectrometry

Semi-Quantitatively Designing Two-Photon High-Performance Fluorescent Probes for Glutathione S-Transferases

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Research 2020年第1期2020卷 1191-1201页

作者： Xue-Xiang Zhang Huan Qi Mei-Heng Lu Song-Qiu Yang Peng Li hai-long piao Ke-Li Han State Key Laboratory of Molecular Reaction Dynamics Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Institute of Molecular Sciences and Engineering Shandong UniversityQingdao 266237China

Glutathione S-transferases(GSTs),detoxification enzymes that catalyze the addition of glutathione(GSH)to diverse electrophilic molecules,are often overexpressed in various tumor *** fluorescent probes for GSTs have often adopted the 2,4-dinitrobenzenesulfonyl(DNs)group as the receptor unit,they usually suffer from considerable background reaction noise with GSH due to excessive electron ***,weakening this reactivity is generally accompanied by loss of sensitivity for GSTs,and therefore,finely turning down the reactivity while maintaining certain sensitivity is critical for developing a practical ***,we report a rational semiquantitative strategy for designing such a practical two-photon probe by introducing a parameter adopted from the conceptual density functional theory(CDFT),the local electrophilicityω_(k),to characterize this *** expected,kinetic studies establishedω_(k)as efficient to predict the reactivity with GSH,and probe NI3 showing the best performance was successfully applied to detecting GST activities in live cells and tissue sections with high sensitivity and signal-to-noise *** electron transfer of naphthalimide-based probes,captured by femtosecond transient absorption for the first time and unraveled by theoretical calculations,also contributes to the negligible background noise.

关键词： reactivity Probe negligible

Supermassive Primordial Black Holes for Nano-Hertz Gravitational Waves and High-redshift JWST Galaxies

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Research in Astronomy and Astrophysics 2024年第9期24卷 1-6页

作者： hai-long Huang Yong Cai Jun-Qian Jiang Jun Zhang Yun-Song piao School of Physical Sciences University of Chinese Academy of SciencesBeijing 100049China Institute for Astrophysics School of PhysicsZhengzhou UniversityZhengzhou 450001China International Centre for Theoretical Physics Asia-Pacific University of Chinese Academy of SciencesBeijing 100190China Taiji Laboratory for Gravitational Wave Universe(Beijing/Hangzhou) University of Chinese Academy of SciencesBeijing 100049China School of Fundamental Physics and Mathematical Sciences Hangzhou Institute for Advanced StudyUCASHangzhou 310024China Institute of Theoretical Physics Chinese Academy of SciencesBeijing 100190China

Recently,observational hints for supermassive black holes have been accumulating,prompting the question:Can primordial black holes(PBHs)be supermassive,particularly with masses M■10^(9)M_(⊙)?A supercritical bubble,containing an inflating baby universe,that nucleated during inflation can evolve into a PBH in our observable *** find that when the inflaton slowly transitions past a neighboring vacuum,the nucleation rate of supercritical bubbles inevitably peaks,leading to a mass distribution of multiverse PBHs with a peak mass up to M■10^(11)M_(⊙).Thus,our mechanism naturally provides a primordial origin for supermassive black holes.

关键词： (cosmology:)early universe (cosmology:)inflation (galaxies:)quasars:supermassive black holes

Cholesterol as a functional metabolite cooperates with metadherin in cancer cells

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Chinese Chemical Letters 2020年第7期31卷 1831-1834页

作者： Wen Wang Xiaolong Liu Huan Chen Ting Ling Tian Xia Xiumei Liu Jing Liu Wuxiyar Otkur Xianzhe Shi Huan Qi Di Chen hai-long piao CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China University of Chinese Academy of Sciences Beijing 100049China

Protein-metabolite interactions(PMIs)play important roles in various biological processes,especially in disease ***,due to the complexity of living cells,it is very difficult to identify specific ***,we chose one oncogenic factor,metadherin(MTDH),as a bait to identify its in vivo interacting metabolites in cancer *** is an important metabolite and essential structural component of cell *** could also drive several diseases including ***,we found that cholesterol robustly interacted with MTDH and downregulated the expression of MTDH in cancer ***,MTDH disturbed metabolite alterations under cholesterol treatment in MTDH transduced cancer ***,our results uncover an undescribed PMI where MTDH,as an oncogenic factor,might positively regulate cancer progression by interacting with choleste *** study interprets the theoretical basis of PMI-oriented cancer progression and targeting therapies in clinic.

关键词： Metabolite-protein interaction Cholesterol Metadherin Mass spectrometry

Metabolomics profiling of metformin-mediated metabolic reprogramming bypassing AMPKα

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Metabolomics profiling of metformin-mediated metabolic repro...

Growth performance,serum parameters,inflammatory responses,intestinal morphology and microbiota of weaned piglets fed 18%crude protein diets with different ratios of standardized ileal digestible isoleucine to lysine

第三届中国生物物理学会代谢生物学分会学术研讨会

作者： Min Yan Huan Qi hai-long piao CAS Key Laboratory of Separation Science for Analytical Chemistry Scientific Research Center for Translational MedicineDalian Institute of Chemical PhysicsChinese Academy of Sciences 中国科学院大连化学物理研究所

Metformin is a first-line drug for treating type 2 diabetes and has gained considerable interest as a potential anticancer *** evidence suggests that metformin antagonizes diabetes and tumors through disrupting metabolic homeostasis and altering energy ***,whether AMP activated protein kinase(AMPK) contributes to such effects of metformin remains ***,we performed integrative metabolomics analyses to systematically examine the effects of metformin on metabolic pathways in Prkaal wild type(WT) and knock-out(KO) mouse embryonic fibroblast(MEF) cells based on gas chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry(CE-MS).Metformin treatment induced metabolic reprogramming and reduced the energy state of both Prkaa1 WT and KO MEF cells,as evidenced by suppressed tricarboxylic acid(TCA) cycle,elevated lactate production as well as decreased NAD/NADH ***,metabolic flux analysis also showed that metformin Ampka-independently increased metabolic flux from glucose to lactate and decreased metabolic flux from acetyl-CoA to TCA cycle as well as from pyruvate to ***,metformin Ampka-dependently upregulated P-Acc but Ampkα-independently inhibited the levels of P-mTOR,P-S6,Lc3,Atgl and P-Erk in MEF ***,we demonstrated that a commonly used AMPK agonist 5-Aminoimidazole-4-carboxamide ribonucleotide(AICAR) and fetal bovine serum(FBS)starvation,as a common model for energy stress,both led to Ampkα-independent metabolism alterations in MEF ***,these effects of metformin were also confirmed in human hepatocellular carcinoma(HCC) cells as well as in MCF10 A shControl and shPRKAAl ***,we found that metformin could obviously inhibit colony conformation of HCC cells in an Ampkα-independent *** data highlight a comprehensive view of metabolomics reprogramming mediated by metformin as well as *** observations suggest that metformin could affect ce

关键词： Metformin Ampk Metabolomics Metabolic flux Independence

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Animal Nutrition 2024年第1期16卷 313-325页

作者： Jian Wang Sujie Liu Jiayu Ma Xiaoli Dong Shenfei long Xiangshu piao State Key Laboratory of Animal Nutrition College of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China Beijing Jingwa Agricultural Science and Technology Innovation Center Beijing101206China CJ International Trading Co. LtdShanghai 201107China

The present study was to explore the Ile requirement of piglets fed 18%crude protein(CP)*** hundred and fifty 28-day-old Duroc×Landrace×Yorkshire piglets(8.37±1.92 kg)were randomly divided into 5 dietary treatments(10 piglets per replicate,5 barrows and 5 gilts per replicate)with 45%,50%,55%,60%,65%standardized ileal digestible(SID)Ile-to-Lys ratios,and the SID Lys was formulated to1.19%.The experimental design consisted of two phases(d 1 to 14 and d 15 to 28).Results showed that average daily gain(ADG)had a tendency to quadratically increase as the SID Ile-to-Lys ratio increased(P=0.09),and the optimum SID Ile-to-Lys ratios required to maximize ADG were 48.33%and 54.63%for broken-line linear model and quadratic polynomial model,*** SID Ile-to-Lys ratios had no significant effects on average daily feed intake and gain-to-feed *** matter(Phain fatty acid-producing bacteria abundance and increased pathogenic bacteria ***,taking ADG as the effect index,the optimum SID Ile-to-Lys ratios of piglets offered 18%CP diets were 48.33%and 54.63%based on two different statistical models,respectively,and the deficiency or excess of lle negative

关键词： Weaned piglet Growth performance Intestinal health Isoleucine Reduced crude protein diet

Mitochondrial YBX1 promotes cancer cell metastasis by inhibiting pyruvate uptake

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Life Metabolism 2023年第6期2卷 28-41页

作者： Huan Chen Ting Ling Di Chen Wenjuan Liu Huan Qi Tian Xia Xiaolong Liu Wen Wang Xin Guo Wuxiyar Otkur Fangjun Wang Zhaochao Xu Jean-Claude Martinou hai-long piao CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalianLiaoning 116023China University of Chinese Academy of Sciences Beijing 100049China Department of Cell Biology University of Geneva1211 GenevaSwitzerland

Pyruvate is an essential fuel for maintaining the tricarboxylic acid(TCA)cycle in the ***,the precise mole-cular mechanism of pyruvate uptake by mitochondrial pyruvate carrier(MPC)is largely ***,we report that the DNA/RNA-binding protein Y-box binding protein 1(YBX1)is localized to the mitochondrial inter-membrane space by its C-terminal domain(CTD)in cancer *** mitochondria,YBX1 inhibits pyruvate uptake by associating with MPC1/2,thereby suppressing pyruvate-dependent TCA cycle *** association,in turn,promotes MPC-mediated glutaminolysis and histone *** findings reveal that the YBX1-MPC axis exhibits a positive correlation with metastatic potential,while does not affect cell proliferation in both cultured cells and tumor ***,the restricted pyruvate uptake into mitochondria potentially represents a hallmark of metastatic capacity,suggesting that the YBX1-MPC axis is a therapeutic target for combating cancer metastasis.

关键词： mitochondria YBX1 pyruvate metabolism MPC1/2 metastasis

YB1 regulates miR-205/200b-ZEB1 axis by inhibiting microRNA maturation in hepatocellular carcinoma

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Cancer Communications 2021年第7期41卷 576-595页

作者： Xiumei Liu Di Chen Huan Chen Wen Wang Yu Liu Yawei Wang Chao Duan Zhen Ning Xin Guo Wuxiyar Otkur Jing Liu Huan Qi Xiaolong Liu Aifu Lin Tian Xia Hong-xu Liu hai-long piao CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalianLiaoning 116023P.R.China Department of Thoracic Surgery Liaoning Cancer Hospital&InstituteCancer Hospital of China Medical UniversityShenyangLiaoning 110042P.R.China Department of Hepatobiliary Surgery The First Affiliated Hospital of Dalian Medical University Dalian Medical UniversityDalianLiaoning 116000P.R.China MOE Laboratory of Biosystem Homeostasis and Protection College of Life SciencesZhejiang UniversityHangzhouZhejiang 310058P.R.China Department of Biochemistry&Molecular Biology School of Life SciencesChina Medical UniversityShenyangLiaoning 110122P.R.China

Background:Y-box binding protein 1(YB1 or YBX1)plays a critical role in tumorigenesis and cancer ***,whether YB1 affects malignant transformation by modulating non-codingRNAs remains largely *** study aimed to investigate the relationship between YB1 and microRNAs and reveal the underlying mechanism by which YB1 impacts on tumor malignancy via miRNAs-mediated regulatory ***:The biological functions of YB1 in hepatocellular carcinoma(HCC)cells were investigated by cell proliferation,wound healing,and transwell invasion *** miRNAs dysregulated by YB1 were screened by microarray analysis in HCC cell *** regulation of YB1 on miR-205 and miR-200b was determined by quantitative real-time PCR,dual-luciferase reporter assay,RNA immunoprecipitation,and pull-down *** relationships of YB1,DGCR8,Dicer,TUT4,and TUT1 were identified by pull-down and coimmunoprecipitation *** cellular co-localization of YB1,DGCR8,and Dicer were detected by immunofluorescent *** in vivo effect of YB1 on tumor metastasis was determined by injecting MHCC97H cells transduced with YB1 shRNA or shControl via the tail vein in nude BALB/c *** expression levels of epithelial tomesenchymal transition markerswere detected by immunoblotting and immunohistochemistry ***:YB1 promoted HCC cell migration and tumor metastasis by regulating miR-205/200b‒ZEB1 axis partially in a Snail-independent ***1 suppressedmiR-205 and miR-200b maturation by interacting with the microprocessors DGCR8 and Dicer as well as TUT4 and TUT1 via the conserved cold shock ***,the downregulation of miR-205 and miR-200b enhanced ZEB1 expression,thus leading to increased cell migration and ***,statistical analyses on gene expression data from HCC and normal liver tissues showed that YB1 expression was positively associated with ZEB1 expression and remarkably correlated with clinical ***:This st

关键词： DGCR8 Dicer hepatocellular carcinoma microRNA maturation YB1 ZEB1

An integrated proteomics and metabolomics strategy to uncover the anti-cancer mechanisms of norcantharidin in hepatocellular carcinoma cells

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An integrated proteomics and metabolomics strategy to uncove...