MECHANISMS OF OXIDATIVE INJURY IN NEURONS & ASTROCYTES

神经元氧化损伤的机制

• 批准号: 3411721
• 负责人: GEORGE A GREGORY
• 金额: $ 11.17万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3411721
• 关键词: astrocytes; fatty acids; fructose biphosphatase; hyperoxia; hypoxia; ion transport; laboratory rat; membrane activity; membrane lipids; membrane structure; metabolism; neurons; peroxidation; respiratory oxygen; tissue /cell culture

Hypoxia and hyperoxia decrease dehydrogenase (LDH) and protein content, cause cell edema, and disrupt cell membranes of primary cultures of astrocytes. Fructose-1, 6-diphosphate (FDP) + glucose (GLc) prevents these changes, but FDP or Glc alone does not. During hypoxia, Na+-K+ ATP-ase activity increases when FDP + Glc is present; it decreases with Glc or FDP alone. We postulate that the protective effects of FDP are either due to increased metabolism and maintenance of normal cellular ion homeostasis or to effects on oxygen free radical production and cell membrane destruction. To test our hypotheses, we will determine whether FDP increases metabolism and ATP content of hypoxic and hyperoxic astrocytes and neurons, whether FDP maintains normal intracellular concentrations of ions, whether FDP prevents cell edema, and whether FDP maintains membrane integrity and function. To determine whether FDP prevents the effects of oxygen free radicals on normoxic and hyperoxic cells, we will determine whether oxygen free radical production increases, whether membrane is altered. Membrane fatty acid composition will also be determined. These studies will provide new information about the effects of hypoxia and hyperoxia on astrocytes and neurons and about the mechanism by which FDP prevents detrimental effects of low and high oxygen. This information will increase our understanding of how cells are injured by abnormal oxygen states and may lead to new methods of brain protection.

缺氧和高氧降低脱氢酶（LDH）和蛋白质 内容物，引起细胞水肿，并破坏细胞膜的初级 星形胶质细胞的培养物。 果糖-1，6-二磷酸（FDP）+葡萄糖 (GLc)阻止这些变化，但FDP或Glc单独不能。 缺氧时，当FDP +时，Na ~+-K ~+ ATP酶活性增加， 存在Glc;单独使用Glc或FDP时，其减少。 我们推测 FDP的保护作用是由于增加了 正常细胞离子稳态的代谢和维持 或对氧自由基产生和细胞膜的影响 杀伤性 为了验证我们的假设，我们将确定 FDP增加缺氧和缺氧大鼠的代谢和ATP含量， 高氧星形胶质细胞和神经元，FDP是否维持正常 细胞内离子浓度，FDP是否阻止细胞 水肿，以及FDP是否维持膜完整性， 功能 为了确定FDP是否能防止 氧自由基对常氧和高氧细胞，我们将 确定氧自由基的产生是否增加， 膜是否改变。 膜脂肪酸组成 也将被确定。 这些研究将提供新的 关于缺氧和高氧对 星形胶质细胞和神经元，以及FDP 防止低氧和高氧的有害影响。 这 这些信息将增加我们对细胞是如何 并可能导致新的方法 大脑保护。