ARYL HYDROCARBON SIGNAL TRANSDUCTION MECHANISMS IN FISH

鱼类中芳基烃信号转导机制

• 批准号: 2414963
• 负责人: WADE H POWELL
• 金额: $ 2.43万
• 依托单位: WOODS HOLE OCEANOGRAPHIC INSTITUTION
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-31 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2414963
• 关键词: aromatic hydrocarbon receptor; biological signal transduction; cycloalkene; molecular cloning; protein structure function; trout /salmon

The overall objective of this project is to understand the molecular mechanisms of the toxic effects of dioxin and other halogenated aromatic hydrocarbons (HAH) in fish, using the estuarine teleost Fundulus heteroclitus as a model system. These compounds are common pollutants which result from many manufacturing processes. Their effects, including tumor promotion, teratogenesis, immunosuppression, and wasting, are mediated through an intracellular receptor. Although the basic scheme of HAH signal transduction is thought to be conserved between vertebrate species, the wide interspecific range of HAH toxicity, the large variation in molecular mass of HAH receptors (AhR) in different species, and the recent discovery of multiple forms of AhR in F. heteroclitus suggest that key differences may exist Specific aims of this project are (1) to clone the aryl hydrocarbon receptor nuclear translocator (ARNT) gene or genes in this species, (2) to characterize interactions between ARNT(s), the multiple AhR forms, and their target DNA sequences, and (3) to identify tissue specific patterns of expression of AhR and ARNT genes which may govern their physiological roles. The study of HAH signal transduction in fish is important for the validation of fish as model systems for in vivo toxicological testing of compounds posing potential human hazards. Knowledge of the molecular mechanisms governing the metabolism and accumulation of HAH compounds in fish will also have important implications for the assessment of the safety of fish consumption by humans and the use of fish as biomarkers for pollutant exposure.

该项目的总体目标是了解分子 二恶英和其他卤代芳香族化合物的毒性作用机制 使用河口硬骨鱼 Fundulus 检测鱼类中的碳氢化合物 (HAH) 异斜体作为模型系统。这些化合物是常见污染物 这是许多制造过程的结果。它们的影响包括 促进肿瘤、致畸、免疫抑制和消瘦， 通过细胞内受体介导。虽然基本方案是 HAH 信号转导被认为在脊椎动物之间是保守的 HAH 毒性的种间范围广、 不同物种中 HAH 受体 (AhR) 的分子质量存在差异， 以及最近在异斜菌中发现的多种形式的 AhR 表明可能存在关键差异 该项目的具体目标是 (1)克隆芳烃受体核转位子(ARNT) 该物种中的一个或多个基因，（2）表征之间的相互作用 ARNT、多种 AhR 形式及其靶 DNA 序列，以及 (3) 鉴定 AhR 和 ARNT 基因的组织特异性表达模式 这可能决定它们的生理作用。 HAH信号的研究 鱼中的转导对于验证鱼作为模型很重要 对具有潜力的化合物进行体内毒理学测试的系统 人类危害。了解控制的分子机制 鱼体内HAH化合物的代谢和积累也会产生影响 对鱼类安全评估具有重要意义 人类消费和使用鱼类作为污染物的生物标志物 接触。