ROLE OF DOCOSAHEXAENOIC ACID METABOLISM IN RETINA

二十二碳六烯酸代谢在视网膜中的作用

• 批准号: 3258836
• 负责人: Nicolas G. Bazan
• 金额: $ 12.64万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-03-01 至 1992-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3258836
• 关键词: Anura; arachidonate; autoradiography; cell biology; cell membrane; chromatography; fatty acid metabolism; laboratory mouse; laboratory rat; linolenate; mass spectrometry; newborn human (0-6 weeks); phagocytosis; retina; retina degeneration; visual photoreceptor

The metabolism and physiological significance of docosahexaenoic acid, a major fatty acid of photoreceptors, remain largely unknown. The present proposal is a continuation of our ongoing studies focusing on several aspects of the cell biology of docosahexaenoic acid metabolism. The hypothesis to be tested is that the supply, uptake and metabolism of docosahexaenoic acid in the visual cell plays a central role in the development, renewal and function of photoreceptor membranes. The proposal follows a postnatal developmental approach to study docosahexaenoic acid metabolism in dissociated rod photoreceptor cells prior, during and after outer segment biogenesis in normal mice and in mice with retinal degeneration. Since docosahexaenoic acid is derived from linolenic acid, an essential fatty acid supplied by the diet, the origin of retinal docosahexaenoic acid, its synthesis from linolenic acid in the liver and its transport via the blood to the retina, will be studied. Another goal of this proposal is to correlate docosahexaenoic acid metabolism with photoreceptor shedding and phagocytosis in the frog. The retina synthesizes docosanoids (22-carbon, leukotriene- like compounds). This proposal will test the hypothesis that these metabolites are involved in signaling mechanisms involved in photoreceptor shedding. Docosanoids formed in response to shedding and the enzymes responsible for docosanoid production will be characterized. The possibility that the docosanoid-producing enzymes are distinct from lipoxygenases involved in arachidonic acid metabolism will be explored. In addition, the subcellular localization of docosanold production will be determined. The approach proposed for these studies combines cell biological techniques (dissociated rod photoreceptor cells, autoradiography and eye cup preparations) with highly sensitive and specific biochemical procedures (high-performance liquid chromatography, capillary gas-liquid chromatography, gas chromatography-mass spectrometry) and should contribute to a better understanding of the role of docosahexaenoic acid in visual cells.

二十二碳六烯酸的代谢及其生理意义 酸，光感受器的主要脂肪酸，在很大程度上仍然未知。 目前的建议是我们正在进行的研究的延续 专注于二十二碳六烯酸的细胞生物学的几个方面， 酸代谢 待检验的假设是， 二十二碳六烯酸在视细胞中的摄取和代谢 在发展、更新和发挥作用方面发挥着核心作用， 感光膜 该提案遵循产后 二十二碳六烯酸代谢研究进展 外照射前、中、后分离的视杆细胞 正常小鼠和视网膜病变小鼠的节段生物发生 退化 由于二十二碳六烯酸是从亚麻酸 脂肪酸，一种由饮食提供的必需脂肪酸， 视黄酸二十二碳六烯酸，由亚麻酸合成， 肝脏和它的运输通过血液到视网膜，将是 研究了 这项提案的另一个目标是将二十二碳六烯酸 代谢与光感受器脱落和吞噬作用， 青蛙 视网膜合成二十二烷类化合物（22碳，白细胞三烯- 类似化合物）。 这一提议将检验以下假设： 代谢物参与信号传导机制， 光感受器脱落 响应脱落形成的二十二烷类化合物 负责产生二十二烷类化合物的酶 表征了 产生类二十二烷酸的可能性 这些酶与花生四烯酸代谢中涉及的脂氧合酶不同。 将探索酸代谢。 此外，亚细胞 将确定docosanold生产的本地化。 为这些研究提出的方法结合了细胞生物学 技术（分离的视杆细胞，放射自显影 和眼杯制剂）具有高度敏感和特异性， 生物化学方法（高效液相色谱法， 毛细管气相色谱-质谱 光谱法），并应有助于更好地了解 二十二碳六烯酸在视觉细胞中的作用。