Rustenbeck I, Eibl H, Lenzen S
Institute of Pharmacology and Toxicology, University of Göttingen, F.R.G.
Biochim Biophys Acta. 1991 Oct 14;1069(1):99-109. doi: 10.1016/0005-2736(91)90109-l.
Analogues of lysophosphatidylcholine, including PAF (platelet-activating-factor) and HePC (an experimental anticancer drug), were studied for their influence on mitochondrial Ca2+ transport and membrane potential. Lysophospholipids released Ca2+ from mitochondria and reduced the maximal Ca2+ uptake. The structure-activity relations indicate that deprotonated head groups like phosphocholines yield active compounds while partially protonated head groups like phosphoethanolamines are essentially inactive. Structural requirements for the apolar part of the molecules were acyl or alkyl chain lengths of less than 18 carbon atoms at the C1-position of the glycerol backbone and residues of small size and/or low polarity at the C2-position. Choline lysophospholipids, but not ethanolamine lysophospholipids, may therefore induce mitochondrial Ca2+ efflux and become mediators of ischaemic tissue damage where dysregulated phospholipase A2 activity and an impairment of mitochondrial function are supposed to play a crucial role.
研究了溶血磷脂酰胆碱类似物，包括血小板活化因子（PAF）和实验性抗癌药物六氢吡啶环已烷甲酸（HePC）对线粒体Ca2+转运和膜电位的影响。溶血磷脂从线粒体释放Ca2+并降低最大Ca2+摄取量。构效关系表明，去质子化的头部基团如磷酸胆碱可产生活性化合物，而部分质子化的头部基团如磷酸乙醇胺基本无活性。分子非极性部分的结构要求是甘油主链C1位的酰基或烷基链长度小于18个碳原子，C2位为小尺寸和/或低极性的残基。因此，胆碱溶血磷脂而非乙醇胺溶血磷脂可能诱导线粒体Ca2+外流，并成为缺血性组织损伤的介质，在这种损伤中，磷脂酶A2活性失调和线粒体功能受损被认为起着关键作用。
