CYCLODIENE INDUCED BINDING PROTEIN

环二烯诱导的结合蛋白

• 批准号: 2019237
• 负责人: David Andrew Johnson
• 金额: $ 9.68万
• 依托单位: EAST TENNESSEE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2019237
• 关键词: binding proteins; chemical binding; chlorohydrocarbon insecticide; environmental toxicology; gene induction /repression; immunocytochemistry; liver metabolism; pesticide biological effect; protein purification; protein sequence; toxin metabolism; trout /salmon

DESCRIPTION: (Adapted from the Investigator's Abstract) Feeding rainbow trout diet containing low concentrations of the cyclodiene insecticide dieldrin increases biliary excretion of a challenge dose of [14C]dieldrin 300-700% and [3H]7,12-dimethylbenz[a]anthracene (DMBA) about 300%. This interaction occurs without evidence of induction of the cytochrome P-450 system, UDP-glucuronyltransferase, or glutathione S-transferases. Precision cut liver slices from dieldrin-fed trout accumulate about two-fold more [14C] dieldrin from medium than slices from control fish. Liver slices from dieldrin fed trout exhibit slightly increased uptake but more markedly stimulated efflux of [3H]DMBA. Preliminary immunohistochemical studies provide no evidence for induction of a multidrug resistance (mdr)-like protein in liver of dieldrin fed rainbow trout. Column chromatography indicates dieldrin increases [3H]DMBA and [3H]benzo[a]pyrene binding protein(s) in rainbow trout hepatic cytosol. The working hypothesis for the proposed research is that dieldrin induces hepatic binding protein(s) important in biliary excretion of anionic metabolites of lipophilic xenobiotics. The rainbow trout is emerging as useful model in research on chemical carcinogenesis and as a sentinel species in assessing status and extent of water contamination. Identifying a binding protein which may be rate limiting in hepatic elimination of some lipophilic xenobiotics would advance mechanistic explanations of their disposition in the rainbow trout model. The objectives for this proposal are to: (1) purify a dieldrin-inducible DMBA binding protein from rainbow trout cytosol; (2) conduct competitive binding assays with this protein; and (3) determine the N-terminal sequence of 20-30 amino acids for this protein.

描述：（改编自研究者摘要）喂养彩虹 含有低浓度环二烯杀虫剂的鳟鱼饲料 狄氏剂增加[14 C]狄氏剂激发剂量的胆汁排泄 300-700%和[3 H] 7，12-二甲基苯并[a]蒽（DMBA）约300%。 这 相互作用发生时没有细胞色素P-450诱导的证据 系统、UDP-葡糖醛酸转移酶或谷胱甘肽S-转移酶。 精度 从喂食狄氏剂的鳟鱼身上切下的肝片， [14C]培养基中的狄氏剂含量高于对照鱼的切片。 肝脏切片 喂食狄氏剂的鳟鱼对狄氏剂的吸收略有增加，但更显著地 [3 H]DMBA的刺激外排。 初步免疫组织化学研究 未提供诱导多药耐药（MDR）样的证据 饲喂狄氏剂的虹鳟鱼肝脏蛋白质含量的变化。 柱色谱 表明狄氏剂增加[3 H]DMBA和[3 H]苯并[a]芘结合 虹鳟鱼肝细胞质中的蛋白质。 关于这一点的工作假设 建议的研究是狄氏剂诱导肝结合蛋白 亲脂性脂蛋白阴离子代谢物在胆汁排泄中重要 异生物质 虹鳟鱼正在成为研究 化学致癌作用，并作为一个哨兵物种，在评估状态， 水污染程度。 鉴定结合蛋白，其可以是 某些亲脂性异生物质的肝脏消除速率限制 对它们在虹鳟鱼中的分布提出了机械的解释 模型 该提案的目标是：（1）净化 虹鳟鱼胞液中的狄氏剂诱导的DMBA结合蛋白;（2） 用该蛋白进行竞争性结合测定;和（3）确定 该蛋白质的N-末端序列为20-30个氨基酸。