Amyloid beta-peptide1-40 increases neuronal membrane fluidity: role of cholesterol and brain region.
Amyloid beta-peptide1-40 increases neuronal membrane fluidity: role of cholesterol and brain region.
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发表时间：
2001-08
影响因子：
6.5
通讯作者：
S. V. Chochina;N. A. Avdulov;U. Igbavboa;J. Cleary;E. O’Hare;W. Wood
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文献类型：
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作者：
S. V. Chochina;N. A. Avdulov;U. Igbavboa;J. Cleary;E. O’Hare;W. Wood
越来越多的证据表明胆固醇动态与阿尔茨海默病（AD）之间存在相互作用，淀粉样蛋白-肽可能在这种相互作用中发挥重要作用。β破坏脑膜的稳定，这种作用可能取决于膜胆固醇的含量。我们通过使用荧光探针芘和能量转移检测Abeta1-40对大鼠大脑皮层、小脑和海马突触质膜（SPM）的环状流动性（即蛋白质附近的脂质环境）和大体积流动性的影响来验证这一假设。测定各脑区SPM的胆固醇和磷脂含量。与大脑皮层和海马的SPM相比，小脑的SPM明显更具流动性。Abeta显著增加大脑皮层和海马SPM的环流动性和体积流动性（P <或= 0.01）。相比之下，β对小脑SPM的环状流动性和整体流动性没有影响。大鼠大脑皮层和海马SPM内胆固醇含量显著高于小脑SPM内胆固醇含量（P <或= 0.05）。与大脑皮层SPM相比，小脑SPM总磷脂含量显著降低（P <或= 0.05）。富含胆固醇的神经元膜可能通过疏水相互作用促进Abeta的积累，这种解释与最近的研究一致，研究表明可溶性Abeta可以在胆固醇存在的情况下作为纤维形成的种子。
There is increasing evidence of an interaction between cholesterol dynamics and Alzheimer's disease (AD), and amyloid beta-peptide may play an important role in this interaction. Abeta destabilizes brain membranes and this action of Abeta may be dependent on the amount of membrane cholesterol. We tested this hypothesis by examining effects of Abeta1-40 on the annular fluidity (i.e., lipid environment adjacent to proteins) and bulk fluidity of rat synaptic plasma membranes (SPM) of the cerebral cortex, cerebellum, and hippocampus using the fluorescent probe pyrene and energy transfer. Amounts of cholesterol and phospholipid of SPM from each brain region were determined. SPM of the cerebellum were significantly more fluid as compared with SPM of the cerebral cortex and hippocampus. Abeta significantly increased (P < or = 0.01) annular and bulk fluidity in SPM of cerebral cortex and hippocampus. In contrast, Abeta had no effect on annular fluidity and bulk fluidity of SPM of cerebellum. The amounts of cholesterol in SPM of cerebral cortex and hippocampus were significantly higher (P < or = 0.05) than amount of cholesterol in SPM of cerebellum. There was significantly less (P < or = 0.05) total phospholipid in cerebellar SPM as compared with SPM of cerebral cortex. Neuronal membranes enriched in cholesterol may promote accumulation of Abeta by hydrophobic interaction, and such an interpretation is consistent with recent studies showing that soluble Abeta can act as a seed for fibrillogenesis in the presence of cholesterol.