Okamoto H, Kawaguchi H, Sano H, Kageyama K, Kudo T, Koyama T, Kitabatake A
Department of Cardiovascular Medicine, Hokkaido University, Sapporo, Japan.
J Mol Cell Cardiol. 1994 Feb;26(2):211-8. doi: 10.1006/jmcc.1994.1024.
To investigate the microdynamics and the structural architecture of the membrane phospholipid bilayer during the course of cardiomyopathy, membrane fractions were prepared from hearts of cardiomyopathic Syrian hamsters (BIO 14.6) aged 4, 18 and 31 weeks and compared with age-matched control hamsters (F1b). Membrane cholesterol, phospholipids and phospholipid fatty acids were measured by thin-layer chromatography, gas-liquid chromatography and high performance liquid chromatography. Microdynamics of the phospholipid bilayer were determined by a nanosecond fluorometer using pulsed excitation of a fluorescent probe, diphenyl-hexatriene. At the age of 4 weeks, there was no difference in lipid compositions and microdynamics between the BIO 14.6 and F1b. At the age of 18 weeks, saturated fatty acids, 18:0 and 22:0 increased and 20:0, 20:2 and 32:4 decreased in the BIO 14.6. At the age of 31 weeks, adding to the above changes in phospholipid fatty acids, unsaturated fatty acids 20:4 and 22:6 decreased, moreover membrane phospholipids, especially phosphatidylinositol and phosphatidylethanolamine significantly decreased. The viscosity and the wobbling angle of phospholipid molecules were decreased significantly. We have previously demonstrated that intracellular Ca2+ accumulation might be responsible for the pathogenesis of cardiomyopathy. Thus, we conclude that cardiomyopathic membrane may alter its structure and function with age. These alterations in cell membranes might be involved in the cardiac hypertrophy and dysfunction through impaired Ca2+ handling in cardiomyopathic hamsters.
为研究心肌病过程中膜磷脂双层的微观动力学和结构架构,从4周龄、18周龄和31周龄的心肌病叙利亚仓鼠(BIO 14.6)心脏中制备膜组分,并与年龄匹配的对照仓鼠(F1b)进行比较。通过薄层色谱法、气液色谱法和高效液相色谱法测量膜胆固醇、磷脂和磷脂脂肪酸。使用荧光探针二苯基己三烯的脉冲激发,通过纳秒荧光计测定磷脂双层的微观动力学。在4周龄时,BIO 14.6和F1b之间的脂质组成和微观动力学没有差异。在18周龄时,BIO 14.6中饱和脂肪酸18:0和22:0增加,20:0、20:2和32:4减少。在31周龄时,除了上述磷脂脂肪酸的变化外,不饱和脂肪酸20:4和22:6减少,而且膜磷脂,尤其是磷脂酰肌醇和磷脂酰乙醇胺显著减少。磷脂分子的粘度和摆动角显著降低。我们之前已经证明细胞内Ca2+积累可能是心肌病发病机制的原因。因此,我们得出结论,心肌病膜可能会随着年龄的增长而改变其结构和功能。这些细胞膜的改变可能通过心肌病仓鼠中Ca2+处理受损而参与心脏肥大和功能障碍。