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Role of Apolipoprotein A-I in Protecting against Endotoxin Toxicity

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Acta Biochimica et Biophysica Sinica 2004年第6期36卷 419-424页

作者： Juan MA, Xue-Ling LIAO, Bin LOU, and Man-Ping WU* Department of Biochemistry, school of pharmacy, fudan university, shanghai 200032, c.ina Department of Biochemistry School of Pharmacy Fudan UniversityShanghai 200032 China

High density lipoprotein (HDL) binds lipopolysaccharide (LPS or endotoxin) and neutralizes its toxicity. We investigated the function of Apolipoprotein A-I (ApoA-I), a major apolipoprotein in HDL, in this process. Mouse macrophages were incubated with LPS, LPS+ApoA-I, LPS+ApoA-I+LFF (lipoprotein-free plasma fraction d>1.210 g/ml), LPS+HDL, LPS+HDL+LFF, respectively. MTT method was used to detect the mortality of L-929 cells which were attacked by the release-out cytokines in LPS-activated macrophages. It was found that ApoA-I significantly decreased L-929 cells mortality caused by LPS treatment (LPS vs. LPS+ApoA-I, Pct became even more significant when LFF was utilized (LPS vs. LPS+ApoA-I+LFF, Pcant difference between LPS+ApoA-I+LFF and LPS+HDL+LFF treatment, indicating that ApoA-I was the main factor. We also investigated in vivo effects ofApoA-I on mouse mortality rate and survival time after LPS administration. We found that the mortality in LPS+ApoA-I group (20%) and in LPS+ApoA-I+LFF group (10%) was signifi- cantly lower than that in LPS group (80%) (Pctively); the survival time was (43.20 ± 10.13) h in LPS+ApoA-I group and (46.80 ± 3.79) h in LPS+ApoA-I+LFF group, which were significantly longer than that in LPS group (16.25 ± 17.28) h (Pcarried out in vitro binding study to investigate the binding capacity of ApoA-I and ApoA-I+LFF to fluorescence labeled LPS (FITc-LPS). It was shown that both ApoA-I and ApoA-I+LFF could bind with FITc-LPS, however, the binding capacity of ApoA-I+LFF to FITc-LPS (6..47 ± 8.06. was significantly higher than that of ApoA-I alone (24.35 ± 3.70) (Pct against LPS; (2) LFF enhances the effect of ApoA-I; (3) ApoA-I is the major contributor for HDL anti-endotoxin function.

关键词： Apolipoprotein-I lipopolysaccharide (LPS) macrophages FITc-lipopolysaccharide (FITc-LPS) L-929 cells

Identification and characterization of glnA Promoter and its corresponding Trans-regulatory Protein GlnR in the Rifamycin SV Producing Actinomycete,Amycolatopsis mediterranei U32

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Acta Biochimica et Biophysica Sinica 2006年第12期38卷 831-843页

作者： Hao YU~(1&) Wen-Tao PENG~1 Yang LIU~1 Ting WU~2 Yu-Feng YAO~1 Ming-Xue cUI~1 Wei-Hong JIANG~1 Guo-Ping ZHAO~(1,3,4*) 1 Laboratory of Molecular Microbiology,Institute of Plant Physiology and Ecology,shanghai Institutes for Biological Sciences,chinese Academy of Sciences,shanghai 200032,c.ina 2 Department of medicinal chemistry,school of pharmacy,{6.,shanghai 200032,c.ina 3 State Key Laboratory of Genetic Engineering & Department of Microbiology,school of Life Science,{6.,shanghai 200433,c.ina 4 Laboratory of Disease and Health Genomics,chinese National Human Genome center at shanghai,shanghai 201203,c.ina Laboratory of Molecular Microbiology Institute of Plant Physiology and Ecology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200032 China Department of medicinal chemistry School of Pharmacy Fudan University Shanghai 200032 China State Key Laboratory of Genetic Engineering & Department of Microbiology School of Life Science Fudan University Shanghai 200433 China Laboratory of Disease and Health Genomics Chinese National Human Genome Center at Shanghai Shanghai 201203 China

The genetic requirements for the transcription of glnA,encoding the major glutaminesynthetase in a rifamycin SV-producing Amycolatopsis mediterranei strain,U32,were *** experiments showed that the promoter of U32 glnA （pglnA） was likely to have two transcriptioninitiation sites:P1and P2,located 157 and 45 nucleotides （nt） upstream of the translational start codon,*** mobility shift and DNase I footprinting analyses revealed a 30 bp cis-element locatedat 45 to 75 nt downstream of P1,or 38 to 6. nt upstream of *** sequence of the cis-element displayedhigh similarity to the corresponding regions of pglnA from Streptomyces coelicolor and *** as a reporter gene,the expression levels of U32 pglnA and its deletion derivatives under differentnitrogen-source conditions were analyzed by detecting the catechol dioxygenase activities in ***54,*** J508 and *** FS10 （glnR mutant）.These in vivo studies showed that theactivation of U32 pglnA in *** required GlnR,and its binding to the U32 pglnA was furtherconfirmed by the gel mobility shift *** and heterologous expression of the U32 glnR allowed usto detect the in vitro interaction between the U32 GlnR and the corresponding pglnA *** shown by in vivo glnR inactivation and complementation indicated that GlnR is essential for theactive transcription of glnA in U32.

关键词： glnA promoter cis-element glnR Amycolatopsis mediterranei

Distribution of nimodipine in brain following intranasal administration in rats

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Acta Pharmacologica Sinica 2004年第4期25卷 124-129页

作者： Qi-zhi ZHANG, Xin-guo JIANG2, chun-hua WU Department of Pharmaceutics, school ofpharmacy, fudan university, shanghai 200032, c.ina Department of Pharmaceutics School of Pharmacy Fudan University

AIM: To determine whether nasally applied nimodipine (NM) could improve its systemic bioavailability and be transported directly from the nasal cavity to the brain. METHODS: NM was administered nasally, intravenously (iv), and orally to male Sprague-Dawley rats. At different times post dose, blood, cerebrospinal fluid (cSF), and brain tissue samples were collected, and the concentrations of NM in the samples were analyzed byHPLc. RESULTS: Oral systemic bioavailability of NM in rats was 1.17 %, nasal dosing improved bioavailibility to 6..4 %. Following intranasal administration, NM concentrations in olfactory bulb (OB) within 30 min post dose were found significant higher than in the other brain tissues. However, similar NM levels in different brain regions were observed after iv injection. AUc in cSF and OB from the nasal route was 1.26.and 1.39 fold compared with the iv route, respectively. The brain-to-plasma AUc ratios were significantly higher after nasal administration than after iv administration (PcONcLUSION: Nasally administered NM could markedly improve the bioavailability and a fraction of the NM dose could be transported into brain via the olfactory pathway in rats.

关键词： intranasal administration nimodipine olfactory bulb olfactory pathways

Structural comparisons of meptazinol with opioid analgesics

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Acta Pharmacologica Sinica 2005年第3期26卷 334-338页

作者： Wei LI Jing-lai HAO Yun TANG Yan cHEN Zhui-bai QIU~2 Department of medicinal chemistry,school of pharmacy,fudan university shanghai 200032,c.ina Departmentofmedicinalchemistry SchoolofPharmacyFudanUniversityShanghai200032China

Aim:To investigate the mechanism of action of a potent analgesic,(±)-***:The structures of meptazinol enantiomers were compared with opioidpharmacophore and ***:Neither enantiomer of meptazinol fittedany patterns among the opioid pharmacophore and tramadol,although they didshare some structural and pharmacological ***,the structuresuperpositions implied that both enantiomers of meptazinol might share somesimilar analgesic mechanisms with typical opiate ***:Meptazinol should have a different mechanism of action to known analgesics,which would be helpful in further investigations of meptazinol in the search fornon-addictive analgesics.

关键词： meptazinol tramadol opioid analgesics pharmacophore

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

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Science c.ina 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 200433,c.ina 2 Institutes of Biomedical Sciences,fudan university,shanghai 200433,c.ina 1. Department of chemistry Fudan University Shanghai 200433 China 2. Institutes of Biomedical Sciences 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

Bacterial Type Ⅰ Glutamine Synthetase of the Rifamycin SV Producing Actinomycete,Amycolatopsis mediterranei U32,is the Only Enzyme Responsible for Glutamine Synthesis under Physiological conditions

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Acta Biochimica et Biophysica Sinica 2006年第12期 821-830页

作者： Wen-Tao PENG~(1&) Jin WANG~1 Ting WU~2 Jian-Qiang HUANG~1 Jui-Shen cHIAO~1 Guo-Ping ZHAO~(1,3,4) 1 Laboratory of Molecular Microbiology,Institute of Plant Physiology and Ecology,shanghai Institutes for Biological Sciences,chinese Academy of Sciences,shanghai 200032,c.ina 2 Department of medicinal chemistry,school of pharmacy,{6.,shanghai 200032,c.ina 3 State Key Laboratory of Genetic Engineering/Department of Microbiology,school of Life Science,{6.,shanghai 200433,c.ina 4 Laboratory of Health and Disease Genomics,chinese National Haman Genome center at shanghai,shanghai 201203,c.ina

The structural gene for glutamine synthetase,glnA,from Amycolatopsis mediterranei U32 wascloned via screening a genomic library using the analog gene from Streptomyces *** clone wasfunctionally verified by complementing for glutamine requirement of an Escherichia coli glnA null mutantunder the control of a lac *** analysis showed an open reading frame encoding a protein of46. amino acid *** deduced amino acid sequence bears significant homologies to other bacterialtype Ⅰ glutamine synthetases,specifically,71% and 72% identical to the enzymes of *** and Myco-bacterium tuberculosis,*** of this glnA gene in *** U32 led to glutamineauxotrophy with no detectable glutamine synthetase activity in *** contrast,the cloned glnA+gene cancomplement for both phenotypes in *** thus suggested that in *** U32,the glnA geneencoding glutamine synthetase is uniquely responsible for in vivo glutamine synthesis under our laboratorydefined physiological conditions.

关键词： glnA glutamine synthetase Amycolatopsis mediterranei rifamycin SV

Induction of systemic lupus erythematosus syndrome in BALB/c mice by immunization with active chromatin

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Acta Pharmacologica Sinica 2004年第6期25卷 105-109页

作者： Hong LI, Yun-yi ZHANG, Ya-nan SUN, Xi-yi HUANG, Yong-feng JIA, Duan LI2 Department of Pharmacology, schoolof pharmacy, fudan university, shanghai 200032, c.ina Department of Pharmacology School of Pharmacy Fudan University Shanghai 200032 China

AIM: To establish an animal model for systemic lupus erythematosus (SLE)-like syndrome in mice. METHODS: BALB/c mice were immunized with active chromatin isolated from conA-actived syngeneic spleno-lymphocytes. Plasma samples of mice were tested by enzyme-linked immunosorbent assays (ELISA) for the presence of IgG anti-dsDNA, -ssDNA, and anti-histone antibodies. Tumor necrosis factor-α (TNF-α) in serum was measured by ELISA. Spleno-lymphocyte proliferation assays and the levels of interferon-γ (IFN-γ) in supernatants were tested respectively. Proteinuria was measured. Kidneys were examined by direct immunohistochemical method and light microscopy. RESULTS: Anti-ds DNA, ssDNA, and histone antibodies were induced in active chromatin-immu- nized mice, the proliferation response of splenocytes to conA and LPS were reduced, levels of interferon-γ in supernatants and TNF-α in serum were lowered. Lupus nephritis was assessed by the presence of Ig deposits, glomerular pathology and proteinuria. cONcLUSION: The active chromatin-induced SLE-like mouse model was similar to idiopathic SLE in human.

关键词： systemic lupus erythematosus chromatin autoantibody tumor necrosis factor interferon type II B-lymphocytes T-lymphocytes female enzyme-linked immunosorbent assay

Impact of Long-term Exposure to Air Particulate Matter on Life Expectancy and Survival Rate of shanghai Residents

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Biomedical and Environmental Sciences 2002年第3期15卷 209-214页

作者： KAN HAI-DONG1 AND cHEN BING-HENG Department of Environmental Health, school of Public Health, fudan university, shanghai 200032, c.ina Department of Environmental Health School of Public Health Fudan University 上海 200032

Objective To evaluate the impact of long-term air particulate matter exposure on the life expectancy and survival rate of shanghai residents. Methods Epidemiology - based exposure-response function was used for the calculation of attributable deaths to air particulate matter in shanghai, and the effect of long-term exposure to particulate matter on life expectancy and survival rate was estimated using the life table of shanghai residents in 1999. Results It was shown that in 1999, the long-term air particulate matter exposure caused 1.34-1.6. years reduction of life expectancy and a decrease of survival rate for each age group of shanghai residents. conclusion The effect of long-term exposure to air particulate matter on life expectancy is substantial in shanghai.

关键词： Particulate matter Life expectancy Survival rate shanghai

Synthesis of adamantane on zeolite catalysts

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chinese Journal of chemistry 1994年第1期12卷 52-57页

作者： GAO, Zi YANG, Xiao-BoDepartment of chemistry, fudan university, shanghai 200433, c.ina Department of chemistry Fudan University Shanghai 200433 China

The synthesis of adamantane from tetrahydrodicyclopentadiene on zeolites with different framework structures was studied. The adamantane yield on HY zeolites is higher than on HM and HZSM-5 zeolites. Among various types of dealuminated HY zeolites the HEY and HUSY zeolites give higher adamantane yields than conventional HY zeolite. The changes in activity and selectivity of the main and side reactions are correlated with the acidity and the pore structure of the zeolites. To ion-exchange the HY and HUSY zeolites with Ni2+ and La3+ cations may further improve the activity and selectivity of the zeolite catalysts.

关键词： Adamantance zeolite catalysis ion-exchange.