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Metalloproteins/metalloenzymes for the synthesis of acetyl-CoA in the Wood-Ljungdahl pathway

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Science China Chemistry 2009年第12期52卷 2071-2082页

作者： ZHU XiaoFei1 & TAN XiangShi1,2.1 Department of Chemistry,fudan university,Shanghai 2.04.3,China 2.{2. of biomedical {4.,fudan university,Shanghai 2.04.3,China 1. Department of Chemistry Fudan University Shanghai 200433 China 2. institutes of biomedical {2. Fudan University Shanghai 200433 China

This paper focuses on the group of metalloproteins/metalloenzymes in the acetyl-coenzyme A synthesis pathway of anaerobic microbes called Wood-Ljungdahl pathway,including formate dehydrogenase (FDH),corrinoid iron sulfur protein (CoFeSP),acetyl-CoA synthase (ACS) and CO dehydrogenase (CODH). FDH,a key metalloenzyme involved in the conversion of carbon dioxide to methyltetrahydrofolate,catalyzes the reversible oxidation of formate to carbon dioxide. CoFeSP,as a methyl group transformer,accepts the methyl group from CH3-H4.folate and then transfers it to ACS. CODH reversibly catalyzes the reduction of CO2.to CO and ACS functions for acetyl-coenzyme A synthesis through condensation of the methyl group,CO and coenzyme A,to finish the whole pathway. This paper introduces the structure,function and reaction mechanisms of these enzymes.

关键词： Wood-Ljungdahl pathway formate dehydrogenase corrinoid iron sulfur protein acetyl-CoA synthase CO dehydrogenase

A meta-analysis of oxidative stress markers in schizophrenia

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中国科学：生命科学英文版 2010年第1期53卷 112-124页

作者： ZHANG Ming1,2.ZHAO ZhongMing3,HE Lin1,2.4.& WAN ChunLing1,2.1 Bio-X Center,Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education),Shanghai Jiao Tong university,Shanghai 2.0030,China 2.institutes for Nutritional {2.,Shanghai Institute of Biological {2.,Chinese Academy of {2.,Shanghai 2.0031,China 3 Departments of biomedical Informatics,Psychiatry,and Cancer Biology,Vanderbilt university Medical Center,Nashville,TN 372.2.USA 4.institutes of biomedical {2.,fudan university,Shanghai 2.0032.China 1. Bio-X Center Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education) Shanghai Jiao Tong University Shanghai 200030 China2. Institutes for Nutritional Sciences Shanghai Institute of Biological Sciences Chinese Academy of Sciences Shanghai 200031 China3. Departments of Biomedical Informatics Psychiatry and Cancer Biology Vanderbilt University Medical Center Nashville TN 37232 USA4. Institutes of Biomedical Sciences Fudan University Shanghai 200032 China

Oxidative stress has been identified as a possible element in the neuropathological processes of schizophrenia(SCZ).Alteration of oxidative stress markers has been reported in SCZ studies,but with inconsistent *** evaluate the risk of oxidative stress to schizophrenia,a meta-analysis was conducted,including five markers of oxidative stress [thiobarbituric reactive substances(TBARS),nitric oxide(NO),catalase(CAT),glutathione peroxidase(GP) and superoxide dismutase(SOD)] in SCZ patients versus healthy *** study showed that TBARS and NO significantly increased in SCZ,while SOD activity significantly decreased in the disorganized type of SCZ *** significant effect size was found for the activities of GP and CAT in SCZ patients(P>0.05).Egger’s regression test observed no significant publication bias across the oxidative stress markers,but found high heterogeneities in all the 5 *** subgroup analysis suggested that the ethnicity,sample size of patients and sample sources may contribute to the heterogeneity of the results for TBARS,NO and *** result further demonstrated the involvement of oxidative stress in the pathophysiology of schizophrenia.

关键词： schizophrenia oxidative stress meta-analysis lipid peroxidation nitric oxide antioxidant enzymes

Recent developments of nanoparticle-based enrichment methods for mass spectrometric analysis in proteomics

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Science China Chemistry 2010年第4期53卷 695-703页

作者： ZHANG LiJuan, LU HaoJie & YANG PengYuan Department of Chemistry and institutes of biomedical {2., fudan university, Shanghai 2.04.3, China 1. Department of Chemistry and institutes of biomedical {2. Fudan University Shanghai 200433 China

In proteome research, rapid and effective separation strategies are essential for successful protein identification due to the broad dynamic range of proteins in biological samples. Some important proteins are often expressed in ultra low abundance, thus making the pre-concentration procedure before mass spectrometric analysis prerequisite. The main purpose of enrichment is to isolate target molecules from complex mixtures to reduce sample complexity and facilitate the subsequent analyzing steps. The introduction of nanoparticles into this field has accelerated the development of enrichment methods. In this review, we mainly focus on recent developments of using different nanomaterials for pre-concentration of low-abundance peptides/ proteins, including those containing post-translational modifications, such as phosphorylation and glycosylation, prior to mass spectrometric analysis.

关键词： enrichment nanoparticles mass spectrometry proteomics phosphorylation glycosylation

Proteomic dissection of biological pathways/processes through profiling protein-protein interaction networks

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Science China Chemistry 2010年第4期53卷 737-746页

作者： CHEN Xian institutes for biomedical {2., fudan university, Shanghai 2.04.3, China Department of Biochemistry & Biophysics, School of Medicine, {4. of North Carolina-Chapel Hill, USA 1. institutes for biomedical {2. Fudan University Shanghai 200433 China2. Department of Biochemistry & Biophysics School of Medicine University of North Carolina-Chapel Hill Chapel Hill USA

Cellular functions, either under the normal or pathological conditions or under different stresses, are the results of the coordinated action of multiple proteins interacting in macromolecular complexes or assemblies. The precise determination of the specific composition of protein complexes, especially using scalable and high-throughput methods, represents a systematic approach toward revealing particular cellular biological functions. In this regard, the direct profiling protein-protein interactions (PPIs) represent an efficient way to dissect functional pathways for revealing novel protein functions. In this review, we illustrate the technological evolution for the large-scale and precise identification of PPIs toward higher physiologically relevant accuracy. These techniques aim at improving the efficiency of complex pull-down, the signal specificity and accuracy in distinguishing specific PPIs, and the accuracy of identifying physiological relevant PPIs. A newly developed streamline proteomic approach for mapping the binary relationship of PPIs in a protein complex is introduced.

关键词： Chen Proteomic dissection of biological pathways/processes through profiling protein-protein interaction networks

Biomarkers of neurodegenerative disorders: How good are they?

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Cell Research 2004年第5期14卷 347-358页

作者： Varun RACHAKONDA Department of Neurology Baylor College of Medicine Houston TX USA

Biomarkers are very important indicators of normal and abnormal biological processes. Specific changes in pathologies, biochemistries and genetics can give us comprehensive information regarding the nature of any particular disease. A good biomarker should be precise and reliable, distinguishable between normal and interested disease, and differential between different diseases. It is believed that biomarkers have great potential in predicting chances for diseases, aiding in early diagnosis, and setting standards for the development of new remedies to treat diseases. New technologies have enabled scientists to identify biomarkers of several different neurodegenerative diseases. The followings, for instance, are only a few of the many new biomarkers that have been recently identified: the phosphorylated tau protein and aggregated β-amyloid peptide for Alzheimer’s disease (AD), α-synuclein contained Lewy bodies and altered dopamine transporter (DAT) imaging for Parkinson’s disease (PD), SOD mutations for familial amyotrophic lateral sclerosis (ALS), and CAG repeats resulted from Huntington’s gene mutations in Huntington’s disease (HD). This article will focus on the most-recent findings of biomarkers belonging to the four mentioned neurodegenerative diseases.

关键词： Alzheimer’s disease Parkinson’s disease Amyotrophic Lateral Sclerosis Huntington’s disease biomarkers.

Effects of Citral on Aspergillus flavus Spores by Quasi-elastic Light Scattering and Multiplex Microanalysis Techniques

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Acta Biochimica et Biophysica Sinica 2004年第4期36卷 277-283页

作者： Man LUO1,2. Li-Ke JIANG2. Yao-Xiong HUANG3, Ming XIAO4. Bo LI4. and Guo-Lin ZOU1* 1College of Life sciences, Wuhan university, Wuhan 4.0072. China 2.ollege of Life sciences, Anhui Agricultural university, Hefei 2.0036, China 3 Institute of {4. Engineering, Ji’nan university, Guangzhou 510632. China 4.inistry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, the Institute of Biodiversity Science, fudan university, Shanghai 2.04.3, China College of Life sciences Wuhan UniversityWuhan 430072 China College of Life sciences Anhui Agricultural UniversityHefei 230036 China Institute of biomedical Engineering Ji'nan UniversityGuangzhou 510632 China Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering the Institute of Biodiversity Science Fudan UniversityShanghai 200433 China

Citral refined from Litsea cubeba oil has been found to have a strong influence on fungi, especially Aspergillus flavus. Multiplex microanalysis and quasi-elastic light scattering techniques were applied to study the effects of citral on Aspergillus flavus spores from the levels of membrane, organelle and intracellular macromolecule. It was found that citral injured the wall and the membrane of A. flavus spore, resulting in decrease of its elasticity. After entering the cell, citral not only influenced the genetic expression of mitochondrion reduplication and its morphology, but also changed the aggregation of protein-like macromolecules. As a result, cells, organelles and macromolecules lost their normal structures and functions, eventually leading to the loss of germination ability of A. flavus spores. Since Litsea cubeba oil as food additive and antifungal agent is safe and less poisonous, it is important to elucidate the inhibitory mechanisms of Litsea cubeba oil on the germination ability of A. flavus spore.

关键词： citral Aspergillus flavus spore multiplex microanalysis techniques quasi-elastic light scattering technique

Effects of astragaloside IV on pathogenesis of metabolic syndrome in vitro

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Acta Pharmacologica Sinica 2006年第2期27卷 229-236页

作者： Ming-en XU~(2.3,4. Shang-zhi XIAO~3 Yong-hong SUN~3 Yang OU-YANG~3 Xiao-xiang ZHENG~(3,4. ~2.epartment of biomedical Engineering,Hangzhou Dianzi university.Hangzhou 310018 ~3Department of biomedical Engineering.Zhejiang university.Hangzhou 31002..China Department of biomedical Engineering Hangzhou Dianzi UniversityHangzhou 310018 China. xumingen@***

Aim:To investigate the diverse pharmacological actions of astragaloside IV fromthe perspective of metabolic syndrome,and to investigate the effect of the drugon the pathogenesis of metabolic ***:Adipogenesis was usedas an indicator of the effect of astragaloside Ⅳ on preadipocyte differentiation,and was measured by using an oil red O *** uptake was determined bymeasuring the transport of [2.3H]-deoxyglucose into the *** concentrationsof peroxisome proliferator-activated receptor-γ（PPARγ）and aP2.mRNA were de-termined by using reverse transcription-polymerase chain *** viability loss of endothelial cells were detected by using flow cytometry andthe WST-1 assay,*** free Ca2.was labeled with Fluo-3 AMand measured by using a laser scanning confocal ***:Astragaloside Ⅳ can significantly potentiate insulin-induced preadipocyte differ-entiation at concentrations of 3,10,and 30 μg/mL,improve high glucose-inducedinsulin resistance in adipocytes at a concentration of 30 μg/mL,and prevent tumornecrosis factor（TNF）-α-induced apoptosis and viability loss at concentrations of10 and 30 μg/mL,and 30 μg/mL,respectively,in endothelial ***,wefound that these effects were partly due to the promotion of PPARγ expressionand to the inhibition of abnormal TNF-α-induced intracellular free Ca2.accumula-tion in endothelial ***:The diverse pharmacological actions ofastragaloside 1V can all be linked to metabolic syndrome *** studyprovides a new insight into the mechanism by which astragaloside Ⅳ exerts itseffect.

关键词： astragaloside Ⅳ metabolic syndrome X insulin resistance peroxisome proliferatoractivated receptors apoptosis calcium

The contribution of cis-regulatory elements to head-to-head gene pairs' co-expression pattern

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Science China(Life sciences) 2009年第1期52卷 74-79页

作者： HAO Pei1,2.YU Yao2.3,ZHANG XiaoYan4.TU Kang2.FAN HaiWei2.& ZHONG Yang1 1 School of Life {4.,fudan {2.,Shanghai 2.04.3,China 2.Bioinformatics Center,Key Lab of Systems Biology,Shanghai institutes for Biological {4.,Chinese Academy of {4.,Shanghai 2.0031,China 3 Shanghai Center for Bioinformation Technology,Shanghai 2.02.5,China 4.School of Life {4.,Tongji {2.,Shanghai 2.0092.China 1. School of Life sciences Fudan University Shanghai 200433 China 2. Bioinformatics Center Key Lab of Systems Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China 3. Shanghai Center for Bioinformation Technology Shanghai 200235 China 4. School of Life sciences Tongji University Shanghai 200092 China

Transcription regulation is one of the most critical pipelines in biological process,in which cis-elements play the role as gene expression *** attempt to deduce the principles underlying the co-expression of "head-to-head" gene pairs by analyzing activities or behaviors of the shared cis-elements.A network component analysis was performed to estimate the impact of cis-elements on gene promoters and their activities under different *** discoveries reveal how biological system uses those regulatory elements to control the expression pattern of "head-to-head" gene pairs and the whole transcription regulation system.

关键词： transcription regulation cis-elements "head-to-head" gene pairs

LOD score exclusion analyses for candidate disease susceptibility genes using case-parents design

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Progress in Natural Science:Materials International 2006年第1期16卷 30-38页

作者： DENG Hongwen1,2.3 and GAO Guimin2.4.(1.Laboratory of Molecular and Statistical Genetics, College of Life sciences, Hunan Normal university, Changsha 4.0081, China 2.Osteoporosis Research Center, Creighton university Medical Center, Omaha NE 68131, USA 3. Department of biomedical sciences, Creighton university, Omaha NE 68131, USA 4. Virginia Bioin format ics Institute and Department of Statistics, Virginia Polytechnic Institute and State university, Blacksburg VA 2.061-0315, USA) [a]Laboratory of Molecular and Statistical Genetics College of Life Sciences Human National University Changsha China [b]Osteoporosis Research Center Creighton University Medical Center Omaha NE USA [c]Department of biomedical sciences Creighton University Omaha NE USA [d]Virginia Bioinformatics Institute and Department of Statistics Virginia Polytechnic Institute and State University Blacksburg VA USA

The focus of almost all the association studies of candidate genes is to test for their importance. We recently developed a LOD score approach that can be used to test against the importance of candidate genes for complex diseases and quantitative traits in random samples. As a complementary method to regular association analyses, our LOD score approach is powerful but still affected by the population admixture, though it is more conservative. To control the confounding effect of population heterogeneity, we develop here a LOD score exclusion analysis using case-parents design, the basic design of the transmission disequilibrium test (TDT) approach that is immune to population admixture. In the analysis, specific genetic effects and inheritance models at candidate genes can be analyzed and if a LOD score is ≤ - 2. 0, the locus can be excluded from having an effect larger than that specified. Simulations show that this approach has reasonable power to exclude a candidate gene having small genetic effects if it is not a disease susceptibility locus (DSL) with sample size often employed in TDT studies. Similar to association analyses with the TDT in nuclear families, our exclusion analyses are generally not affected by population admixture. The exclusion analyses may be implemented to rule out candidate genes with no or minor genetic effects as supplemental analyses for the TDT. The utility of the approach is illustrated with an application to test the importance of vitamin D receptor (VDR) gene underlying the differential risk to osteoporosis.

关键词： association studies candidate genes case-parents design disease susceptibility locus exclusion mapping LOD score.