PAF ACETYLHYDROSE & CONTROL OF PEROXIDATIVE DAMAGE TO SPERM MEMBRANES

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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.