Photooxidative Damage in Cell Membranes

细胞膜易受结构和功能损伤 当在光敏颜料存在下照射时。 一 这种损害的主要形式是脂质过氧化， 导致流动性改变、渗透性增加等 方面的影响. 光敏脂质过氧化反应 系统在反应途径方面还没有得到很好的研究， 细胞毒性作用和保护/修复机制。 整体 这项研究的目的是提高我们对 膜脂过氧化反应在这些领域的每一个。 一 全面和多样化的工作计划，使用 模型系统最初（脂质体，红细胞膜）和 然后培养细胞（鼠L1210细胞）。 致敏剂 感兴趣是非结合的尿卟啉和膜结合的 原卟啉和血卟啉衍生物（HPD）。 模型 研究：（a）计划开展涉及胆固醇的广泛工作 (Ch)作为I型（自由基）与II型的原位探针 （单线态氧）脂质过氧化途径。 （B） 抗坏血酸对光引发的脂质过氧化作用的放大作用 将从面向系统的角度进行研究，例如： 过氧化氢和氧自由基的影响。 (c)远程 过氧化作用（敏化剂和靶脂质分开 膜隔室）将首次进行研究。 （d）其他事项 光过氧化物的还原代谢（解毒）将是 检查，使用谷胱甘肽还原酶/过氧化物酶系统。 细胞研究：（a）第一个实验，利用Ch作为一个 活细胞中的机械探针将使用（14 C- HPD致敏的L1210细胞中的Ch。 (b)的关系 将通过以下方法研究光过氧化和细胞致死性：（i） 比较脂质过氧化物含量和存活率，和（ii） 确定谷胱甘肽或谷胱甘肽的消耗 过氧化物酶影响光敏性。 脂质过氧化作用的生化机制及其对肝纤维化的影响 生物膜的完整性和功能非常重要， 重要的根本性。 将得到的信息 这项研究将对提高我们的基础 了解不同领域的知识，如光 与光感受器相互作用， 杀死细菌，以及培养细胞的原因，当研究 在光学显微镜下观察一段时间， 与生物体中的细胞不同。

Cell membranes are subject to structural and functional damage when irradiated in the presence of photosensitizing pigments. A prominent form of such damage is lipid peroxidation, which can result in altered fluidity, increased permeability, and other effects. Photosensitized lipid peroxidation in biological systems has not been well studied in terms of reaction pathways, cytotoxic effects, and protective/repair mechanisms. The overall objective of this research is to improve our understanding of membrane lipid peroxidation in each of these areas. A comprehensive and diversified program of work is planned, using model systems initially (liposomes, erythrocyte membranes) and then cultured cells (murine L1210 cells). The sensitizers of interest are non-bound uroporphyrin, and membrane-bound protoporphyrin and hematoporphyrin derivative (HPD). Model Studies: (a) Extensive work is planned involving cholesterol (Ch) as an in situ probe of Type I (free radical) vs Type II (singlet oxygen) pathways of lipid peroxidation. (b) Amplification of photoinitiated lipid peroxidation by ascorbate will be investigated from a system-oriented perspective, e.g. effects of hydrogen peroxide and oxyradicals. (c) Long-range peroxidation (with sensitizer and target lipid in separate membrane compartments) will be studied for the first time. (d) Reductive metabolism (detoxification) of photoperoxides will be examined, using the glutathione reductase/peroxidase system. Cell Studies: (a) The first experiments to exploit Ch as a mechanistic probe in living cells will be carried out using (14C- Ch in HPD-sensitized L1210 cells. (b) The relationship between photoperoxidation and cytolethality will be investigated by (i) comparing lipid peroxide content and survivability, and (ii) determining how depletion of glutathione or glutathione peroxidase affects photosensitivity. The biochemical mechanisms and effects of lipid peroxidation on the integrity and function of biological membranes is of very great fundamental importance. Information that will be derived from this research will have implications in enhancing our basic knowledge of such diverse areas as the mechanisms by which light interacts with photoreceptors, the mechanisms by which leukocytes kill bacteria, and the reasons that cultured cells, when studied under the light microscope for periods of time, may behave differently from cells in the organism.