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Acta Pharmacologica Sinica 2004年第4期25卷 33-37页

作者： Xing-mei ZHANG, GangLIU, Man-ji SUN2 Institute of Pharmacology and toxicology, Academyof MilitaryMedical Sciences, Beijing 100850, China Institute of Pharmacology and toxicology Academy of Military Medical Sciences

AIM: To construct synthetic antigens using the epitope of human brain acetylcholinesterase (hbAChE) for induc- tion and detection of the specific antibody against the epitope, and to analyse the immunogenicity of the antibody. METHODS: The epitope (RTVLVSMNYR, amino acids 143-152) of hbAChEwas chemically synthesized, coupled with the carrier protein keyhole limpet hemocyanin (KLH) to construct an artificial immunogen (KLH-epitope), and injected into rabbits to raise antibody. The epitope conjugated with bovine serum albumin (BSA) was used as the detection antigen. The specificity of the antibody was tested by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The immunoreaction between the anti-recombinant human butyrylcholinesterase (rhBChE) polyclonal antibody and the biotinylated-epitope was examined by indirect ELISA. RESULTS: The erythrocyte AChE, the hbAChE, rhBChE and the BSA-epitope all immunoreacted with the anti-epitope antibody against the epitope (143-152) of hbAChE, whereas the torpedo AChE did not. CONCLUSION: The hbAChE, the human erythrocyte AChE and hBChE share the conservative antigenic epitope RTVLVSMNYR, hence they can all immunoreact with the anti-epitope antibody. Since the epitope of hbAChE is less similar with the aligned amino acid sequences of AChE of Torpedo californica or Torpedo marmorata, there is not any immunoreactivity between them. The R, M, and N residues in the epitope seem to be necessary radicals for the conservation of antigenicity.

关键词： acetylcholinesterase butyrylcholinesterase epitopes antibodies enzyme-linked immunosorbent assay Western blotting

SYNTHESIS　AND　ANTICHOLINERGIC　ACTIVITIES　OF　6，11－DIHYDRODIBENZ［b，e］OXEPIN　AND　6，11－DIHYDRODIBENZO［b，e］THIEPIN　HYDROXYCARBOXYLATES

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Chinese Chemical Letters 1996年第2期7卷 115-118页

作者： Shou Hai GAO Liu Hong YUN(Institute of Pharmacology and toxicology,Academy of Military Medical Sciences,Beijing 100850) Inst. of Pharmacology and toxicology Academy of Military Medical Sciences Beijing 100850 China

New tricyclic hydroxycarboxylates-dibenz[b,e]oxepin and dibenzo[b,e]thiepin hydroxycarboxylates (7) were synthesized by modifying the structures of xanthene compounds. The pharmacological results showed the antagonistic activities of these tricyclic compounds were all decreased at different levels after this modification, but they exhibited more selective action on the central nicotinic receptor. Especially, the compounds containing sulfur atom almost have no action on the muscarinic receptors, they were still quite potent to the central niacinic receptor.

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Synthesis of Salmon Calcitonin Analogs Using Fmoc-based Chemistry on MBHA Resins

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Chinese Chemical Letters 1999年第7期10卷 549-552页

作者： Bin YANG Zhen Kai DING Zong Jin HAN Qi Kai ZHANG(Beijing Institute of Pharmacology and toxicology, Beijing 100850) Beijing Inst Pharmacol & Toxicol Beijing 100850 Peoples R China

Peptide analogs of salmon calcitonin (sCT) were synthesized by using Fmoc-based chemistry on MBHA resins. Salmon calcitonin was modified by 1) cysteines at positions 1 and 7 were replaced by valine and alanine respectively to result in open chain analogs, 2) the glycine at position 30 was replaced by alanine, D-alanine and sarcosine respectively, and 3) some residues were deleted besides the above two modifications. A modified two-step deprotection / cleavage procedure, in which a solvent of TFA / TMSBr / thioanisole / EDT / m-cresol combines with HF cleavage, was adopted in SPPS.

关键词： salmon calcitonin analogs Fmoc-based SPPS MBHA resin the two-Step deprotection/cleavage procedure

Chelation in Metal Intoxication XLIV: Efficacy of α-Mercapto β-(5-Substituted, 2-Furyl) Acrylic Acids in Mobilizing Intracellularly Bound Cadmium in Rat

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Biomedical and Environmental Sciences 2000年第3期13卷 205-212页

作者： SUSHIL K. TANDON\+1, SATGUR PRASAD, AND SURENDRA SINGH Industrial toxicology Research Centre, Lucknow_226001, India Industrial toxicology Research Centre M.G. Marg Post Box 80 Lucknow-226001 India

The efficacy of α mercapto β (2_furyl) acrylic acid (MFA), α mercapto β (5_sodiumsulfonate, 2_furyl) acrylic acid (MSFA) and α mercapto β (5_acetoxymethyl, 2_furyl) acrylic acid (MAFA) to mobilize intracellularly bound cadmium in liver and kidney was investigated in rats pre_exposed to cadmium. MFA was effective in reducing cadmium levels of hepatic and renal supernatant cytosolic fraction (SCF) while MSFA and MAFA were effective in lowering cadmium levels of renal SCF and hepatic SCF respectively. All the chelating agents also enhanced the excretion of cadmium more in feces than in urine. However, substitution on the furan ring lowered cadmium mobilizing efficacy of the parent compound, MFA. The treatment with MFA did not affect the status of endogenous zinc and copper while the treatment with MSFA and MAFA enhanced their excretion. MSFA increased hepatic and renal zinc and renal copper while MAFA increased their copper levels.

关键词： Mercapto Substituted Chelation in Metal Intoxication XLIV Furyl Intracellularly Bound Cadmium in Rat Efficacy of Acrylic Acids in Mobilizing

Underlying mechanism of ASIC1a involved in acidosis-induced cytotoxicity in rat C6 glioma cells

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Acta Pharmacologica Sinica 2007年第11期28卷 1731-1736页

作者： Xie-chuan WENG,Jian-quan ZHENG~2,Jin LI,Wen-bin XIAOBeijing Institute of Pharmacology and toxicology,Beijing 100850,China g Institute of Pharmacology and toxicology Beijing 100850 China. wengxc2002@***.

Aim:To investigate the underlying mechanism of acid-sensing ion channel (ASIC)la involved in the acidosis-induced cytotoxicity of rat C6 glioma ***:The stable ASIC 1 a-silenced C6 cells built with the RNA interference technologywere confirmed by RT-PCR and Western blot *** calcium([Ca2+]i) in both the wild-type rat C6 glioma cells and the ASIC 1a-silenced C6 cellswere analyzed before and after acid application/exposure with the calcium ***:The rapid extracellular pH drop induced the increase of[Ca2+]iin the wild-type C6 cells,but not in the ASIC1a-silenced C6 *** prolonged acid exposure,[Ca2+]iwas lower in the ASIC 1 a-silenced C6 cellsthan that in the control ***:The resultant toxicity of [Ca2+]imightcontribute to the acidosis-induced cytotoxicity.

关键词： acid-sensing ion channel calcium calcium imaging Fluo-3

A New Concept in the Control of Iron Deficiency:Community-based Preventive Supplementation of At-Risk Groups by the Weekly Intake of Iron Supplements

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Biomedical and Environmental Sciences 1998年第1期11卷 46-60页

作者： FERNANDO E. VITERI(Deportment of Nutrilional Sciences and toxicology, University ofCalifornia at Berkeley and United Nations Uliversity,Berkeley 94720, Chlifornia, USA) Department of Nutritional Sciences and toxicology University of California at Berkeley USA.

Iron deficiency (ID), defined as an insufficient supply of iron to the cells of the body after iron reserves have been exhausted, is the most prevalent single nutritional deficiency, affecting over 2, 000 million people, mostly in the developing world. Infants, small children, adolescents and pregnant and fertile-age women are most vulnerable. Only about 50 % of people with ID develop iron deficiency anemia (IDA), since this is a late manifes tation of chronic ID. Based on the average daily iron requirement and on the rate of iron reutilization from red cell hemoglobin destruction, it can be estimated that after iron stores have been depleted, it takes about 4 months of ID erythropoiesis for adult women to have a drop in hemoglobin concentration [Hb] of 10 g/l, if the iron intake is only 70 % of requirement. IDA can be defined by a [Hb] below an appropriate cut-off point for age,sex, physiological condition and altitude above sea level, or by a [Hb] increment of morethan 10 g/l to the administration of adequate doses of iron. More than 85 % of the nutritional anemias are IDA alone, or of iron combined with folate or other nutrient deficiencies [WHO/UNICEF/UNU, 1997; Yip, 1994].

关键词： A New Concept in the Control of Iron Deficiency ACC

Effects of methylmercury chloride on the brain chromatin structure in rats at various developing stages

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吉林大学学报(医学版) 1997年第3期 4-7页

作者： Li Zhichao,Li Yong′an,Bi Xiaoying (Department of toxicology) \ \

妊娠７～１１ｄ的孕鼠，经腹腔连续注入氯化甲基汞（２ｍｇ／ｋｇ体重），采用Ｈｅｗｉｓｈ和Ｂｕｒｇｏｙｎｅ法分离纯化不同发育阶段新生大鼠的脑细胞核，来探讨氯化甲基汞对其脑染色质结构的影响。接触或不接触氯化甲基汞的大鼠脑细... 详细信息

妊娠７～１１ｄ的孕鼠，经腹腔连续注入氯化甲基汞（２ｍｇ／ｋｇ体重），采用Ｈｅｗｉｓｈ和Ｂｕｒｇｏｙｎｅ法分离纯化不同发育阶段新生大鼠的脑细胞核，来探讨氯化甲基汞对其脑染色质结构的影响。接触或不接触氯化甲基汞的大鼠脑细胞核分别经ＤＮａｓｅ１和ＥｃｏＲ１核酸内切酶消化后进行缺口翻译。结果接触氯化甲基汞生后３ｄ的大鼠脑细胞核３Ｈ－ｄＡＭＰ的掺入量明显低于相应未接触氯化甲基汞的对照组（Ｐ＜０．０５）。我们认为氯化甲基汞对大鼠发育过程中脑染色质结构的影响可能与胎、幼鼠对甲基汞神经毒性的易感有密切关系。

关键词： Methylmercury chloride Rat Brain chromatin

Actions of Sodium Fluoride on Acetylcholinesterase Activities in Rats

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Biomedical and Environmental Sciences 1998年第1期11卷 1-6页

作者： ZHAO Xi-LONG AND WU J-HONG(Department of Environmental toxicology, Institute of EnvironmentalHealth Minitoring, Chinese Academy of PreventiveMedicine, Beijing 100021, China) Department of Environmental toxicology Chinese Academy of Preventive Medicine Beijing China.

This study was carried out to observe the effects of sodium fluoride on acetylcholinesterase (AChE) activities in the cerebral synaptic membranes (SPM) and the peripheral red blood cells (RBC) of rats by in vivo and in vitro experiments. In the in vivo study,pregnant rats ingested ad libitum fluorinated drinking water (5, 15, 50 ppm F ) during their gestation and lactation. It was shown that the AChE activities of the SPM and peripheral RBCs in maternal rats exposed 5 ~ 50 ppm F for 60 days were elevated significantly by 30. 0 ~ 67. 6 % and 12. 5 ~ 31. 9 % in a dose-dependent manner, respectively. The AChE activities of their offspring 80 days after birth were also increaased (8. 7 ~ 28. 7 % for SPM and20. 6 ~ 32. 4 % for RBC). In contrast, the AChE activities of SPM in vitro were inhibited by 5. 0~ 50 .0 mmol F /L treatment in a time-and dose dependent manner. Analaysis with the Hanes plots suggested that the enzymesubstrate kinetics are consistent with a mixed type ofinhibition.

关键词： Actions of Sodium Fluoride on Acetylcholinesterase Activities in Rats

Effects of Cadmium on the Energy Metabolism of Isolated Hepatocytes: Its Relationship with the Nonviability of Isolated Hepatocytes Caused by Cadmium

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Biomedical and Environmental Sciences 1990年第3期3卷 251-261页

作者： LIU RUINING AND LIU YUGU Department of Environmental toxicology, Tongji Medical University, Wuhan, Hubei Province, China Department of Environmental toxicology Tongji Medical University Wuhan Hubei Province China.

The effects of cadmium on the energy metabolism of mitochondria were studied with isolated hepatocytes and rat liver mitochondria. It was found that cadmium inhibited the respiration of both isolated hepatocytes and mitochondria and decreased the ATP content of isolated hepatocytes. This inhibition of energy metabolism of mitochondria was highly related to the nonviability of isolated hepatocytes caused by cadmium. The site of electron transport of the mitochondrial respiratory chain blocked by cadmium was located between cytochrome b and flavoproteins. The uncoupling effects of mitochondrial oxidative phosphorylation caused by cadmium may have resulted from changes in the fluidity and permeability of the mitochondrial membrane. (c) 1990 Academic Press. Inc.

关键词： Effects of Cadmium on the Energy Metabolism of Isolated Hepatocytes