OXIDANT STRESS, EICOSANOIDS, AND IMMUNE FUNCTIONS

氧化应激、类二十烷酸和免疫功能

• 批准号: 2075232
• 负责人: C CHANNA REDDY
• 金额: $ 15.03万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-01 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2075232
• 关键词: biological response modifiers; biological signal transduction; cell cycle; cellular immunity; cytokine receptors; enzyme linked immunosorbent assay; fatty acid biosynthesis; flow cytometry; high performance liquid chromatography; interleukin 2; laboratory mouse; leukotrienes; lymphocyte; macrophage; nitric oxide; northern blottings; nuclear runoff assay; nutrient requirement; nutrition related tag; oxidative stress; prostaglandins; selenium; transferrin receptor; vitamin E deficiency; western blottings

As a part of our continuing interest in the molecular mechanisms underlying the antioxidant defense functions of vitamin E and selenium (Se), we will undertake a detailed investigation into the role dietary vitamin E and Se status can influence prostaglandin (PG) and leukotriene (LT) biosynthesis in cells associated with the immune system, and that this altered eicosanoid synthesis is involved in the impairment of a number of critical mononuclear cell activities including signal transduction, cytokine production, and cell proliferation. These hypotheses are based on the premise that vitamin E and Se can modulate the synthesis of PGs and LTs. Vitamin E is a free radical scavenger and Se-dependent glutathione peroxidase (Se-GSH-Px) is a key component of an enzyme system involved in the reduction of fatty acid hydroperoxides (FAHPs). These micronutrients can control eicosanoid biosynthesis because free radicals and FAHPs are prerequisites for cyclooxygenase and lipoxygenase, key enzymes involved in the catalysis of rate-limiting steps in PG and LT biosynthesis, respectively. The proposed experiments will be conducted using C57BL/6J mice fed on diets supplemented with or deficient in vitamin E, Se, or both. The specific aims are: 1) to determine the consequences of dietary vitamin E and/or Se deficiency on PG and LT levels in macrophages and lymphocytes; 2) to evaluate the potential relationships between eicosanoid biosynthesis, biological response modifier production, and altered functional capabilities of mononuclear cells during vitamin E and/or Se deficiencies; 3) to examine the effects of vitamin E and/or Se deficiencey on interleukin-2 and transferrin receptor expression on the surface of mononuclear cells; and 4) to examine the potential relationships between eicosanoid production and intracellular signalling and proliferation by lymphocytes in vitamin E and/or Se deficiency states. Molecular probes will be employed to determine whether the effects of inadequate vitamin E and/or Se nutrition on cytokine production, nitric oxide levels, and receptor expression are at the translational or transcriptional levels. Additional experiments are designed to investigate the mechanisms that may explain the decreased proliferative and cytotoxic capabilities of mononuclear cells by vitamin E and/or Se deficiency. Results of these studies will advance our understanding of the influence of oxidant stress, such as that found in vitamin E and/or Se deficient states, on important host defense mechanisms and will provide a molecular basis for the role of eicosanoids on essential immune cell functions.

作为我们对分子机制的持续兴趣的一部分 维生素E和硒的抗氧化剂防御功能（SE），我们将 对饮食维生素E和SE的作用进行详细研究 地位可以影响前列腺素（PG）和白三烯（LT）生物合成 在与免疫系统相关的细胞中，这改变了 eicosanoid合成涉及许多关键的损害 单核细胞活性，包括信号转导，细胞因子 生产和细胞增殖。 这些假设基于 维生素E和SE可以调节PG和LT的合成的前提。 维生素E是一种自由基清除剂和SE依赖性谷胱甘肽 过氧化物酶（SE-GSH-PX）是涉及的酶系统的关键组成部分 脂肪酸氢过氧化物（FAHPS）的还原。 这些微量营养素 可以控制类类生物合成，因为自由基和fahps是 环氧合酶和脂氧合酶的先决条件，涉及的关键酶 PG和LT生物合成中限速步骤的催化， 分别。 提出的实验将使用饮食中的C57BL/6J小鼠进行 补充或缺乏维生素E，SE或两者。 具体 目的是：1）确定饮食中维生素E和/或SE的后果 巨噬细胞和淋巴细胞中PG和LT水平的缺乏； 2）到 评估eicosanoid生物合成之间的潜在关系， 生物响应修饰符的产生和功能改变 维生素E和/或SE缺乏期间单核细胞的能力； 3）检查维生素E和/或SE缺陷对不足的影响 白介素-2和转铁蛋白受体表达在表面上 单核细胞； 4）检查 类类生产和细胞内信号传导和增殖 维生素E和/或SE缺乏状态的淋巴细胞。 分子探针 将采用用于确定维生素E的影响是否不足 和/或SE营养有关细胞因子的产生，一氧化氮水平和 受体表达在翻译或转录水平。 其他实验旨在研究可能的机制 解释降低的增殖和细胞毒性能力 维生素E和/或SE缺乏的单核细胞。 这些结果 研究将促进我们对氧化应激的影响的理解， 例如在维生素E和/或SE缺乏状态中发现的， 宿主防御机制，将为角色提供分子基础 基本免疫细胞功能上的类花生酸酯。