PAF ACETYLHYDROSE & CONTROL OF PEROXIDATIVE DAMAGE TO SPERM MEMBRANES

PAF乙酰氢

• 批准号: 6123277
• 负责人: JOHN E PARKS
• 金额: --
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6123277
• 关键词: biomaterials; biomedical resource; growth /development; health care; male; reproductive system; spectrometry; structural biology

The long-term objective O?'f our research is to understand the physiological relevance of sperm membrane lipid composition and factors that modify and perturb it. A factor that has emerged as especially damaging to sperm and a leading cause of defective sperm function is lipid peroxidation. Mechanisms leading to the generation and propagation of lipid peroxides and their damaging effects are documented but less is known about mechanisms to limit the damage once peroxidation has begun. Recent reports demonstrate that membrane phospholipids cleaved during oxidative degradation provide a unique substrate for a special phospholipase A2, PAF acetylhdyrolase (PAF-A-H), which recognizes damaged lipids within the membrane and selectively hydrolyses them, leaving normal phospholipids intact. Upon peroxidative degradation, the ether-linked, polyunsaturated phosphohpids characteristic of mammalian sperm provide the most important substrate for this enzyme. We have determined that the specific activity of PAF-AH in bovine seminal plasma is ca. 40- to 50-fold higher than that reported for any other biological fluid andthat seminal plasma selectively hydrolyses structural analogues of oxidatively fragmented pbospholipids. We propose that this enzyme plays an important role in limiting peroxidative damage to sperm, as well as the undesirable release of bioactive lipids with PAF-like activity during sperm transport in the female reproductive tract. Specific aims of this research project are to:(1) Characterize the molecular species resulting from peroxidative degradation of sperm membrane and their effect on sperm viability; (2) Determine the substrate specificity of oxidatively damaged sperm PLs for PAF-AH; (3) Characterize the production of PAF-AH in seminal plasma andits relationship to sperm function and fertility; and (4) Purify PAF-AH from seminal plasma to characterize further its effects on sperm membrane structure and function.

我们研究的长期目标是了解 精子膜脂质成分的生理相关性和 改变和扰乱它的因素。 一个因素已经出现 对精子尤其有害，是精子缺陷的主要原因 功能是脂质过氧化。 导致生成的机制 脂质过氧化物的繁殖及其破坏作用 有记录，但对于限制一次损害的机制知之甚少 过氧化反应已经开始。 最近的报告表明，膜 磷脂在氧化降解过程中裂解提供了独特的 特殊磷脂酶 A2、PAF 乙酰水解酶的底物 (PAF-A-H)，识别膜内受损的脂质并 选择性地水解它们，使正常磷脂保持完整。 过氧化降解后，醚连接的多不饱和 哺乳动物精子的磷脂特性提供了最多的 该酶的重要底物。 我们已经确定 牛精浆中PAF-AH的比活性约为。 40-至 比报道的任何其他生物液体高 50 倍 精浆选择性地水解结构类似物 氧化断裂的磷脂。 我们建议这种酶 在限制精子过氧化损伤方面发挥着重要作用， 以及 PAF 类生物活性脂质的不良释放 精子在女性生殖道中运输过程中的活动。 本研究项目的具体目标是：（1）表征 精子过氧化降解产生的分子种类 膜及其对精子活力的影响； (2) 确定 氧化损伤精子 PL 对 PAF-AH 的底物特异性； (3) 表征精浆及其中 PAF-AH 的产生 与精子功能和生育能力的关系； (4) 纯化PAF-AH 从精浆中进一步表征其对精子的影响 膜的结构和功能。