Identification of Li+ binding sites and the effect of Li+ treatment on phospholipid composition in human neuroblastoma cells:: A 7Li and 31P NMR study
Identification of Li+ binding sites and the effect of Li+ treatment on phospholipid composition in human neuroblastoma cells:: A 7Li and 31P NMR study
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DOI：
10.1016/j.bbadis.2005.07.004
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发表时间：
2005-09-25
影响因子：
6.2
通讯作者：
de Freitas, DM
中科院分区：
文献类型：
--
作者：
Layden, BT;Abukhdeir, AM;de Freitas, DM
利用Li-7核磁共振自旋-晶格（T-1）和自旋-自旋（7,）弛豫测量研究了Li+在人神经母细胞瘤SH-SY5Y细胞亚细胞组分中的结合，因为T-1/T-2比值是Li+结合的敏感参数。从Li+结合常数和T-1/T-2比值的值可以看出，Li+的结合主要发生在质膜、微粒体和核膜部分，它们比细胞质、细胞核和线粒体中观察到的大得多。我们还通过P-31核磁共振光谱研究了慢性Li+处理4-6周对质膜和细胞匀浆磷脂组成的影响，发现两组磷脂酰肌醇和磷脂酰丝氨酸水平分别显著升高和降低。根据这些观察，我们提出Li+结合主要发生在膜结构域，并且长期Li+处理改变了这些膜位点的磷脂组成。这些发现支持了临床研究表明Li+治疗双相患者会导致Li+结合和磷脂代谢的不规则性。我们对Li+作用的推测机制，包括细胞膜异常、肌醇耗竭和g蛋白假说的观察意义进行了讨论。(c) 2005 Elsevier B.V.版权所有
Li+ binding in subcellular fractions of human neuroblastoma SH-SY5Y cells was investigated using Li-7 NMR spin-lattice (T-1) and spin-spin (7,) relaxation measurements, as the T-1/T-2 ratio is a sensitive parameter of Li+ binding. The majority of Li+ binding occurred in the plasma membrane, microsomes, and nuclear membrane fractions as demonstrated by the Li+ binding constants and the values of the T-1/T-2 ratios, which were drastically larger than those observed in the cytosol, nuclei, and mitochondria. We also investigated by P-31 NMR spectroscopy the effects of chronic Li+ treatment for 4-6 weeks on the phospholipid composition of the plasma membrane and the cell homogenate and found that the levels of phosphatidylinositol and phosphatidylserine were significantly increased and decreased, respectively, in both fractions. From these observations, we propose that Li+ binding occurs predominantly to membrane domains, and that chronic Li+ treatment alters the phospholipid composition at these membrane sites. These findings support those from clinical studies that have indicated that Li+ treatment of bipolar patients results in irregularities in Li+ binding and phospholipid metabolism. Implications of our observations on putative mechanisms of Li+ action, including the cell membrane abnormality, the inositol depletion and the G-protein hypotheses, are discussed. (c) 2005 Elsevier B.V. All rights reserved.