LEAD EFFECT ON ION TRANSPORT IN FATHEAD GILL

铅对黑头鳃中离子传输的影响

• 批准号: 2728511
• 负责人: ERIC G SPOKAS
• 金额: $ 11.93万
• 依托单位: UNIV OF MED/DENT NJ-SCH OSTEOPATHIC MED
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2003-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2728511
• 关键词: Osteichthyes; cytochrome P450; eicosanoid metabolism; environmental toxicology; gills; ion transport; laboratory rat; lead poisoning; lipid peroxides; oxidative stress; oxygen consumption; peroxidation; renal tubular transport; respiratory epithelium; sodium potassium exchanging ATPase; species difference

The objective of this proposal is to evaluate the effect of chronic lead exposure (water-borne divalent lead) on sodium, potassium ATP-ase (NaK- ATP-ase) activity and membrane lipids in the gill of the fathead minnow Pimephales promelas. The working hypothesis is that low concentrations of soluble lead (added to aquarium water will profoundly influence gill cation transport mechanisms and eicosanoid metabolism. This hypothesis will be tested in aquarium experiments wherein adult fathead minnows will be exposed to selected concentrations of lead (2-10 ppb, as lead nitrate) for up to 3 months. Long term objectives of the Principal Investigator are to characterize this specialized ion transport epithelium in terms of similarities and differences with mammalian systems. The information thus obtained may shed light on the mechanism for chronic lead nephropathy in humans, a disease with unknown etiology. Initial efforts will focus on aquarium studies, including dose-ranging to assess the effects of lead on overall health status as well as the concentration-dependence of alterations of NaK-ATP-ase. Subsequently, the Principal Investigator will carry out time-course studies of effects of lead on gill ATP-ases and oxygen-consumption (basal and ouabain- inhibitable) to determine whether the sodium pump of gill epithelium is more susceptible to inhibition by lead relative to other gill ATP-ases. The ability of chronic lead exposure to cause lipid peroxidation injury to gill membranes will also be explored, using various indices of oxidative damage, including isoprostane production. In the final stage of the project, the effects of lead on ouabain-inhibitable oxygen consumption, lipid peroxidation and eicosanoid metabolism (cytochrome P450 pathway) in gill epithelium will be compared with those obtained in ex vivo studies with isolated renal proximal tubules from rats chronically administered lead in drinking water.

本提案的目的是评估慢性铅中毒的影响 暴露（水媒二价铅）对钠、钾ATP酶（NaK- 黑头呆鱼鳃的ATP酶活性和膜脂 黑头呆鱼 工作假设是低浓度 可溶性铅（添加到水族馆的水会深刻影响鳃 阳离子转运机制和类花生酸代谢。 这一假设 将在水族馆实验中进行测试， 将暴露于选定浓度的铅（2-10 ppb， 硝酸盐）长达3个月。 校长的长期目标 研究者将描述这种专门的离子转运 与哺乳动物的相似性和差异 系统. 由此获得的信息可能有助于阐明 用于人类慢性铅肾病，一种病因不明的疾病。 最初的努力将集中在水族馆的研究，包括剂量范围 评估铅对整体健康状况的影响， NaK-ATP酶改变的浓度依赖性。 随后，委员会注意到， 主要研究者将对效果进行时程研究 铅对鳃ATP酶和耗氧量（基础和哇巴因- 以确定鳃上皮的钠泵是否 相对于其他鳃ATP酶，更容易受到铅的抑制。 慢性铅暴露致脂质过氧化损伤的能力 鳃膜也将探讨，使用各种指数 氧化损伤，包括异前列腺素的产生。 在最后阶段 铅对哇巴因可吸收氧的影响 消耗，脂质过氧化和类花生酸代谢（细胞色素 P450通路）的研究结果进行比较， 在离体大鼠肾近端小管研究中 饮用水中长期摄入铅。