NITRIC OXIDE AS A CELLULAR ANTIOXIDANT

描述（由申请人提供）：有很大的兴趣的作用， 一氧化氮（NO）在生物学中的作用，因为它可以是一种信号分子，一种毒素， 助氧化剂和潜在的抗氧化剂。它涉及： 血管舒张和神经传递，作为一种毒素在病原体的破坏， 并作为脂质和脂质结构中的潜在链断裂抗氧化剂。 在脂质过氧化过程中，NO可以作为链终止抗氧化剂。我们 将测试一氧化氮可能是一个重要的链断裂的假设， 细胞膜中的抗氧化剂;一氧化氮保护细胞膜 自由基介导的脂质过氧化可能造成的损害。 维生素E传统上被认为是主要的小分子， 生物脂质结构中的断链抗氧化剂。但这 在不包括硝酸的实验系统中建立了一个范例 环氧因此，我们也将测试一氧化氮可以作为，或 甚至比维生素E更重要为了验证这个假设，我们将：1。 确定一氧化氮的浓度是需要减缓或停止 自由基介导的细胞内脂质过氧化的连锁反应， 将其与细胞脂质中以氧为中心的自由基的通量联系起来 结构; 2.确定维生素E和一氧化氮的相对重要性 作为细胞脂质结构中的断链抗氧化剂; 3.确定 如果一氧化氮作为一种链断裂抗氧化剂， 保护细胞免受自由基介导的脂质致死性损伤 过氧化作用细胞中脂质过氧化的抑制将在 一种动力学的基础，所以定量比较的能力，一氧化氮和 维生素E作为断链抗氧化剂可以完成。这 项目将提供具体的动力学信息，以帮助阐明的作用， 一氧化氮在与脂质过氧化相关的疾病状态中的作用。

DESCRIPTION (provided by applicant): There is great interest in the role of nitric oxide (NO) in biology because it can be a signaling molecule, a toxin, a pro-oxidant and a potential antioxidant. It is involved in: signaling in vasodilation and neurotransmission, as a toxin in the destruction of pathogens, and as a potential chain-breaking antioxidant in lipids and lipid structures. NO can serve as a chain-terminating antioxidant during lipid peroxidation. We will test the hypothesis that nitric oxide can be an important chain-breaking antioxidant in cellular membranes; nitric oxide protects cell membranes from the damage that can be rendered by free radical-mediated lipid peroxidation. Vitamin E has traditionally been thought to be the principal, small-molecule, chain-breaking antioxidant in biological lipid structures. However, this paradigm was established in experimental systems that did not include nitric oxide. Thus, we will also test the hypothesis that nitric oxide can be as, or even more, important than vitamin E. To examine this hypothesis we will: 1. Determine the concentration of nitric oxide that is required to slow or stop the free radical-mediated chain reactions of lipid peroxidation in cells and relate this to the flux of oxygen-centered radicals in cellular lipid structures; 2. Determine the relative importance of vitamin E and nitric oxide as chain-breaking antioxidants in the lipid structures of cells; 3. Determine if nitric oxide, when serving as a chain-breaking antioxidant, is able to protect cells from lethal damage induced by free radical mediated lipid peroxidation. The inhibition of lipid peroxidation in cells will be analyzed on a kinetic basis so quantitative comparisons of the ability of nitric oxide and vitamin E to serve as chain-breaking antioxidants can be accomplished. This project will provide concrete kinetic information to help elucidate the role of nitric oxide in disease states that have associated lipid peroxidation.