NITRIC OXIDE AS A CELLULAR ANTIOXIDANT

描述(由申请人提供)：人们对……的角色非常感兴趣 生物中的一氧化氮(NO)，因为它可以是一种信号分子，一种毒素，一种 促氧化剂和潜在的抗氧化剂。它涉及：信令传入 血管扩张和神经传递，作为破坏病原体的毒素， 并在脂质和脂质结构中作为潜在的断链抗氧化剂。 在脂质过氧化过程中，NO可作为链终止抗氧化剂。我们 将检验这一假设，即一氧化氮可以是一种重要的断链 细胞膜中的抗氧化剂；一氧化氮保护细胞膜免受 自由基介导的脂质过氧化所造成的损害。 维生素E传统上被认为是主要的小分子物质， 生物脂结构中的断链抗氧化剂。不过，这个 范式是在不包括硝酸盐的实验系统中建立的 氧化物。因此，我们还将测试一氧化氮可以是AS或 比维生素E更重要的是，为了检验这一假说，我们将：1. 确定减速或停止所需的一氧化氮浓度 自由基介导的细胞内脂质过氧化的链式反应和 这与细胞脂质中以氧为中心的自由基流量有关 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.测定 如果一氧化氮在作为一种断链抗氧化剂时能够 保护细胞免受自由基介质脂的致死性损伤 过氧化。对细胞内脂质过氧化的抑制作用将被分析 定量比较一氧化氮和丙二醛能力的动力学基础 维生素E作为断链抗氧化剂是可以做到的。这 项目将提供具体的动力学信息，以帮助阐明 与脂质过氧化有关的疾病状态中的一氧化氮。

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.