FUNCTION OF CARDIOLIPIN PHASE POLYMORPHISM

心磷脂相多态性的功能

• 批准号: 3354273
• 负责人: GARY L POWELL
• 金额: $ 5.86万
• 依托单位: CLEMSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-04-01 至 1990-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3354273
• 关键词: X ray crystallography; cardiolipins; cations; cytochrome oxidase; electron microscopy; freeze etching; ionic strengths; lipid structure; membrane activity; membrane lipids; membrane model; membrane permeability; mitochondrial membrane; nuclear magnetic resonance spectroscopy; phase change

Cardiolipin can be shifted from lamellar phase in low salt concentrations to hexagonal II phase in high salt. Acyl cardiolipin and monolysocardiolipin remain hexagonal II phase or lamellar respectively independent of salt concentration (Powell & Marsh, Biochemistry 24 (1985) 2902-2908). The effects of lamellar- favoring lipids like dioleoylphosphatidylcholine (DOPC) and the presence of the intrinsic membrane enzyme, cytochrome oxidase, on these phase changes will be evaluated using 31P-NMR, low angle X- ray diffration, and freeze-fracture electron microscopy in collaboration with D. Marsh, Max-Planck Institute for Biophysical Chemistry. The permeability of mixtures of DOPC and the above cardiolipins as large unilamellar vesicles to Na, K and 11- will then be measured under conditions in which the phase behavior is known and the effect of incorporating cytochrome oxidase on these permeabilities observed. The results will demonstrate the efficiency of sealing at the lipid protein-interface and the importance of the presence of lipids which form non-lamellar phases to these related membrane properties. In heart tissue lysolipids formed during myocardial infarct probably makes the inner mitochondrial membrane leaky, uncoupling electron transport and phosphorylation directly resulting in cell death. Demonstration of the molecular basis of cell death under these circumstances would ensble better intervention and treatment of patents with heart disease.

在低盐条件下，心磷脂可从片层相中迁移 在高盐浓度下转变为六方II相。 酰基 心磷脂和单溶血心磷脂保持六方II相，或 层状分别独立于盐浓度（Powell & Marsh，Biochemistry 24（1985）2902-2908）。 层状结构的影响- 有利于脂质，如二油酰磷脂酰胆碱（DOPC）和 存在的内在膜酶，细胞色素氧化酶， 这些相变将使用31 P-NMR，低角X-射线衍射， 射线衍射和冷冻断裂电子显微镜， 与D合作。 马克斯-普朗克生物物理研究所 化学. DOPC和上述物质的混合物的渗透性 心磷脂作为大的单层囊泡对Na，K和11- Will 然后在相位特性被 已知的和掺入细胞色素氧化酶对这些细胞的影响 观察到的渗透率。 结果将证明， 在脂质蛋白质界面处的密封效率和 形成非层状相的脂质存在的重要性 这些相关的膜特性。 在心脏组织溶脂中 在心肌梗塞时形成的， 线粒体膜渗漏、解偶联电子传递和 磷酸化直接导致细胞死亡。 示范 在这种情况下细胞死亡的分子基础 将有助于更好地干预和治疗专利， 心脏病