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检索条件"任意字段=中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议"

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The activation mechanism of STING-dependent interferon responses to intracellular DNA in antiviral innate immune signaling pathway

The activation mechanism of STING-dependent interferon respo...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者：欧阳松应刘志杰中国科学院生物物理研究所

The innate immune response is the first line of defense initiated against the *** receptors,contained on the surface or within the cell,named pattern recognitionreceptors(PRRs),recognize molecules that are broadly shared by pathogens but distinguishablefrom host molecules,collectively referred to as pathogen-associated molecularpatterns(PAMPs).The detection of intracellular DNA has emerged as a key event in theinnate immune response to viruses and intracellular bacteria,and during conditions ofsterile inflammation and *** of the consequences of the detection of DNAas a‘stranger’and a‘danger’signal is the production of type I interferons and *** efforts are being made to understand the mechanismsof the recognition of innate immune system to intracellular *** major academicachievements of our group include the clarification of the following points:1)the structuralbasis for recognization of small molecules such as bis-(3',5')-cyclic dimeric guanosinemonophosphate(c-di-GMP)by STING and the molecular mechanisms of TBK1 activationafter pathogen infection(Ouyang et al,Immunity.2012);2)the structural and functionalbasis for activation of TLR9 signaling pathway and its negative regulation(Zhao et al,CellRes.2014;Niu et al,Protein Cell.2014);3)DDX41 can sense both DNA and cyclic dinucleotides(Parvatiyar et al,Nat Immunol.2014);4)NLRC3,a member of the NLR family ofproteins,is a negative regulator of innate immune signaling induced by STING(Zhang etal,Immunity.2014);5)the development of potential drugs for autoimmune diseasescaused by the improper recognition of DNA(Ouyang et al,JMM.2012).

关键词： STING(STimulator of INterferon Genes) molecular mechanisms innate immunity

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Rapamycin promotes Glt1 expression and glutamate uptake inastrocyte

Rapamycin promotes Glt1 expression and glutamate uptake inas...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者：王雪琴许琪中国医学科学院基础医学研究所医学分子生物学重点实验室

Objective: Accumulating evidence indicates that inhibition of the mammalian target ofrapamycin(mTOR) pathway activation in rodent models of epilepsy has antiepileptogeniceffects, but the underlying mechanism is still unknown. Our previous study found that themTOR pathway is activated in astrocytes in mesial temporal sclerosis. We hypothesizedthat blocking the mTOR pathway in astrocyte could promote glutamate uptake by increasingGlt1 protein ***: We treated cultured astrocytes with 5nM rapamycin for 48 hours, then analysedthe expression of glutamate transporters Glt1, Xct and GS by western blot. Meanwhile,after rapamycin treated, adding 22 micromoles glutamate to the medium of astrocytes todetect the rapid reduction of extracellular glutamate by Glutamic acid/Glutamate OxidaseAssay Kit. Moreover, construction shRNA lentivirus S6, TSC1 and 4EBP1 to knockdown S6,TSC1 and 4EBP1 expression in astrocytes before analysed the Glt1 change by western ***: Rapamycin treated to inhibit mTOR passway increases the expression of proteinGlt1 to 1.8 fold and accelerates the rate of extracellular glutamate uptake to 2.1 folds, S6 knockdown increase Glt1 expression and TSC1 knockdown decrease Glt1 expression, bothhave a positive correlation with the declination of extracellular glutamate. However, Glt1 level shows no significant difference with 4EBP1 ***: we identify that mTOR acts as a negative regulator in regulating the expressionof Glt1 and glutamate uptake via S6 passway.

关键词： Glt1 rapamycin glutamate uptake astrocyte

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A New Multiplex Assay of 20 In Del loci for Forensic Application

A New Multiplex Assay of 20 In Del loci for Forensic Applica...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者：王鹏翔李存保严江伟内蒙古医科大学基础医学院中国科学院北京基因组研究所

Objective The pupose of the study is to develop a new multiplex assay of 20 InDel loci forforensic application, which could offer an effective, rapid method to detect degraded *** 20 InDel Locis from Human Genome Browser and dbSNP database which hasgood frequency distribution has been choosed, and all selected InDel markers distributedin the human autosomes, X and Y chromosome. Multiplex PCR systems of 20 selected In-Del markers were developed. The PCR production was genotyping using the long thinnon-denaturing polyacrylamide gels with EB staining, and also genotyping with ABI3130 XL Genetic Analyzer. A series of validation experiments were performed for the InDelmultiplex system. Results 20 InDel multiplex was successfully constructed, and the multiplexis stable and dependable. By the validation detection, we can draw the conclusion: thesensitivity of the system was 0.3ng template DNA. Its species specificity and tissue identitywere good. After using the degraded DNA template, it was showed that the multiplex systemhad a high successful rate for analysis of the degraded DNA. Conclusion A new multiplexassay of 20 InDel loci for forensic application was successfully structured and provedto be reliable which could offer a new effective way to analyse the degraded DNA.

关键词： polymerase chain reaction multiplex PCR insertion/deletion polymorphismd egraded DNA fluorescence labeling

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An Analysis of Protein Bioinformatics Datasets Related to LewyBodies of Parkinson's Disease

An Analysis of Protein Bioinformatics Datasets Related to Le...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者： Xing-An LI Lin-Sen HU Key Laboratory for Honeybee Genetics and (Queen) Breeding Jilin Provincial Institute of Apicultural Science Laboratory for Proteomics Department of Neurology First Affiliated Hospital Jilin University

Lewy bodies(LBs) in dopaminergic neurons in substantia nigra pars compacta(SNpc) arethe cardinal pathological hallmark of Parkinson' disease(PD), while LBs and/ or Lewy neuritesare also seen in non-dopaminergic neurons in other brain regions of patients with PD,such as noradrenergic neurons in locus coeruleus(LC), and cholinergic neurons in prefrontalcortex(PFC) and temporal cortex(TC). To explicit protein contents of LBs in PD,here is an article that demonstrates five aspects of protein constitution of LBs by analyzingprotein bioinformatics datasets related to LBs in PD: 1, LBs is filled with 2 types of alpha-synuclein(α-SYN) positive fibrilar aggregates and/or 6 types of α-SYN positive nonfibrilaraggregates(described frequently in literature as oligomers);2, modification formsof pathological α-SYN in LBs are often associated with 5 species of chemical modifiers;3,19 α-SYN-associated proteins rich in LBs are respectively colocalized with α-SYN;4, 117 previously reported proteins in LBs in immunochemistry study are at least classified into 10 different groups of functional proteins with close relationship;5, proteomics database asprotein candidate resource for LBs contain 84, 124 and 120 proteins identified respectivelyfrom raw tissue samples of LC, SNpc and PFC regions, and 108 proteins identified from acellular separation of analyte captured from TC region, and 29 proteins identified from asub-cellular fraction of analyte isolated from TC region. It is suggested that the aforementionedaspects comprehensively and fundamentally reflect protein composition of LBs inPD.

关键词： Parkinson' disease Lewy bodies proteins bioinformatics

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Screening Novel Inhibitors of Ornithine Decarboxylase, the key Enzyme in Polyamine Biosynthesis

Screening Novel Inhibitors of Ornithine Decarboxylase, the k...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者： Jingqiong Zhan Qian Li Bo Li Yanlin Wang Sen Liu Institute of Molecular Biology/College of Medical Science China Three Gorges University

The nature polyamines(putrescine, spermidine, and spermine)are ubiquitous polycationicalkylamines that play essential roles in many biological processes. Studies showed thatthe rapid growth of tumor cells needs a higher concentration of the intracellular polyaminesthan normal cells. It is also widely accepted that the dysregulation of polyamine metabolismcould cause malignant transformation of cells. Hence, polyamine metabolic pathwayis considered to be a promising target for antitumor *** decarboxylase(ODC) is the first rate-limiting enzyme in regulating intracellularpolyamine biosynthesis, and involved in many important physiological functions, includingembryonic development, cell cycle, cell proliferation and differentiation. At the same time,ODC is also needed by tumor cells for their rapid growth and proliferation. Currently,ODChas been used as a potential molecular target for anti-tumor ***, an irreversible inhibitor of ODC, is used at present in clinic, and can inhibit thegrowth of tumor cells. However, DFMO is not effective enough to warrant continued phaseII trials. Therefore, it has important clinical significance to explore new ODC inhibitors. Inour study, based on the ODC crystal structure, we are trying to select new ODC inhibitorsfrom the small molecule chemical database by computer simulation and experimental *** our virtural screening, we got 90 potential inhibitors. Among these compounds,our experiment confirmed that the compound D24 significantly inhibits A549 cell growthin cell-based assays, and can inhibit ODC enzyme activity as well. Further studies on thepotential mechanism are in progress.

关键词： polyamine metabolism Ornithine decarboxylase ODC inhibitors

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Notch signaling pathway regulates the polarization of macrophages and impact on the progression of tumor

Notch signaling pathway regulates the polarization of macrop...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者：叶雨辰秦鸿雁韩骅窦科峰第四军医大学西京医院肝胆外科第四军医大学基础部遗传与发育教研室

Objective:In the past few years,researchers have discovered that macrophages plays anpivotal role in chronic inflammatory diseases,such as *** macrophages participatein tumor progression and what molecular mechanisms orchestrate the function of macrophages,however,is yet unclear. We created tumor models based on WT C57BL/6 mice(WTmice) and mice with RBPJ specifically knocked-out in macrophages(KO mice),to observedthe effect of notch signaling blockade in macrophages on tumor development,andmoreover,the functional alteration of macrophages,aiming at searching for innovative targetfor medication of ***:We created models of subcutaneously inoculated lung cancer on WT mice andKO mice and observed the difference of tumor *** in percentage of immunecells,polarization of macrophages and expression of relative cytokines in tumor were respectivelydetected by FACS analysis,Immunofluorescent staining,and Quantitative ***:It was discovered that the subcutaneous tumor of KO mice is smaller than that ofWT *** expected,FACS analysis showed that the percentage of TAM of KO mice ***'s more,it was revealed by Immunofluorescent staining and Q-PCR that TAMin KO mice was more inclined to polarize towards an M1-like ***:Progression of subcutaneously inoculated lung cancer could be suppressed byspecific blockade of notch signaling in *** TAM formation and a moreM1-like state could account for this ***,targeting notch signaling inmacrophages might be a promising medication of cancer.

关键词： Notch信号通路巨噬细胞肿瘤肺癌

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Comprehensive Profiling of Accessible Surface Glycans of Mammalian Sperms Using a Lectin Microarray

Comprehensive Profiling of Accessible Surface Glycans of Mam...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者： Li Cheng Ai-Jie Xin Hui-Juan Shi Sheng-Ce Tao Shanghai Center for Systems Biomedicine Key Laboratory of Systems Biomedicine (Ministry of Education) Shanghai JiaoTong University Shanghai Jiai Genetics & IVF Institute Obstetrics and Gynecology Hospital of Fudan University Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases

It is well known that cell surface glycans or glycocalyx play important roles in sperm motility,maturation and fertilization. A comprehensive profile of the sperm surface glycans willgreatly facilitate both basic research（sperm glycobiology） and clinical studies, such as diagnosticsof infertility. As a group of natural glycan binders, lectin is an ideal tool for cellsurface glycan profiling. However, because of the lack of effective technology, only a fewlectins have been tested for lectin-sperm binding profiles. To address this challenge, wehave developed a procedure for high-throughput probing of mammalian sperm with 91 lectins on lectin microarrays. Normal sperm from human, boar, bull, goat and rabbit werecollected and analyzed on the lectin microarrays. Positive bindings of a set of 0 lectinswere observed for all the sperm of 5 species, which indicated a wide range of glycans areon the surface of mammalian sperm. Species specific lectin bindings were also *** analysis revealed that the distances of the five species according to the lectinbinding profiles are consistent with that of the genome sequence based phylogenetic treeexcept for rabbit. The procedure that we established in this study could be generally applicablefor sperm from other species or defect sperm from the same species. We believethe lectin binding profiles of the mammalian sperm that we established in this study arevaluable for both basic research.

关键词： sperm glycocalyx surface glycan lectin microarray

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PIAS1 regulates systemic insulin sensitivity by inhibiting inflammation response

PIAS1 regulates systemic insulin sensitivity by inhibiting i...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者：刘洋葛辛汤其群复旦大学上海医学院

Over the last decade, an abundance of evidence has emerged demonstrating a close linkbetween metabolism and immunity. It is now clear that obesity is associated with a state ofchronic low-level inflammation. Obesity-induced inflammation contributes to diabetes. It iswell recognized that PIAS1(Protein Inhibitor of Activated STAT 1), a SUMO(small ubiquitinlike modifier) E3 ligase, modulates such cellular processes as cell proliferation, DNAdamage responses, and inflammation responses. Recent studies have shown that PIAS1 also involves in adipocyte differentiation and energy metabolism. However, the role of PIAS1 in insulin sensitivity remains unknown. Here we showed that PIAS1 protected bodyfrom insulin resistance induced by gene deficit or high fat diet. PIAS1 was downregulatedin the adipose tissue of diabetic models, including ob/ob, db/db and DIO mice. Ectopic expressionof PIAS1 in diabetic adipose tissue improved systemic insulin sensitivity. Similareffect of PIAS1 was shown in 3T3-L1 adipocytes. Cellular inflammation response may bethe underlying mechanism. We found that PIAS1 inhibited expression of NF-κB targetgenes, mainly including inflammation genes. Furtherstudies clarified that PIAS1 inhibitedmacrophage infiltration in adipose tissue, thus suppressing inflammation response. In conclusion,PIAS1 improved systemic insulin sensitivity by inhibiting cellular inflammation.

关键词： PIAS1 insulin sensitivity inflammation

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Progranulin A9D mutation functionally leads to the cytoplasmretardation of angiogenin

Progranulin A9D mutation functionally leads to the cytoplasm...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者： Siqi Li Yongdui Chen Jinghao Sheng Haojie Dong Guangdi Chen Zhengping Xu Research Center for Molecular Medicine Zhejiang University School of Medicine

Neurodegenerative diseases are progressive neurological disorders with selective neuronloss in particular regions of brain,including frontotemporal lobar degeneration(FTLD),Alzheimer’s disease(AD),amyotrophic lateral sclerosis(ALS),Parkinson’s disease(PD),and many *** defects have been recognized as a prominent factor in the etiologyand pathogenesis of neurodegenerative *** date,hundreds of genetic variantsthat located in dozens of genes have beenassociated with susceptibility to various *** them,more than 60 mutations in progranulin(PGRN)havebeen reported in FTLD,AD,ALS and *** of the mutations in PGRN gene exon 1 introducesa charged amino acid in the hydrophobic core of the signal peptide at residue 9(PGRN A9D),and results in cytoplasmic mis-sorting of this ***,the mechanismof actions of this mis-sorting remains *** address this issue,we first examinedthe subcellular distribution of PGRN with A9D mutation in human neuronal-like cells(SHSY5Y).The results have shown that PGRN A9D mutation failed to undergo maturation andaccumulated in the stress ***,this mutation also induces redistributionof cellular angiogenin(ANG),a stress response factor and neurodegenerative diseases relatedprotein,from nuclear to *** was also directly interacted with ANG instress ***,the cytoplasmic retardation of ANG by PGRN A9D mutationabolished ANG-enhanced rRNA transcription and cell *** together,these resultsindicate that PGRN with A9D mutation changed localization of ANG as well as cellgrowth and survival,suggesting that PGRN and ANG act in concert to regulate the progressof neurodegenerative diseases.

关键词： Progranulin Neurodegenerative diseases Angiogenin stress granule

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The reverse effect of hypoxic pulmonary hypertension of Rhodiolaalgida var. tangutica and related influence on gene expression andprotein content of ET-1、eNOS

The reverse effect of hypoxic pulmonary hypertension of Rhod...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者：芦殿香 Research center of high altitude medicine Qinghai University medical college

The reverse effect of hypoxic pulmonary hypertension(HPH) of Rhodiola algida *** was researched. The hemodynamic changes were recorded and right ventricularhypertrophy index [RV/(LV+S)%] were calculated. The lung tissues were stained by HE andmorphological parameter of vascular wall thickness(WT%) was used to assess the remodelingof small pulmonary arteries. The mRNA and protein levels of endothelin 1(ET-1) andendothelial nitric oxide synthase(eNOS) were measured by Real-time PCR and *** with the control groups, the high dose of Rhodiola algida var. tangutica showedthe pharmacologic actions as follows: 1 The development of mean pulmonary arterialpressure(mPAP), right ventricular hypertrophy index(RV/LV+S), hemoglobin(Hb),haematocrit(Hct)(%) were inhibited( p<0.01);2 The muscularization and vascular wallthickness(WT%) of pulmonary small artery decreased( P<0.05);3 The levels of ET-1mRNA decreased and the levels of eNOS mRNA increased in lung(P<0.05). 4 The levels ofET-1 protein content decreased and the level of eNOS protein content increased in sera(P<0.05). It can be concluded that Rhodiola algida var. tangutica attenuate hypoxic pulmonaryhypertension and remodeling of pulmonary small artery in HPH rats. The mechanismswere related to increase the mRNA and protein level of eNOS and to decrease thelevel of ET-1.

关键词： ET-1 eNOS Rhodiola algida var.tangutica hypoxic pulmonary hypertension

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