Layden Brian T, Abukhdeir Abde M, Malarkey Christopher, Oriti Lisa A, Salah Wajeeh, Stigler Claire, Geraldes Carlos F G C, Mota de Freitas Duarte
Department of Chemistry, Loyola University Chicago, 6525 North Sheridan Road, Chicago, Illinois 60626, USA.
Biochim Biophys Acta. 2005 Sep 25;1741(3):339-49. doi: 10.1016/j.bbadis.2005.07.004.
Li(+) binding in subcellular fractions of human neuroblastoma SH-SY 5 Y cells was investigated using (7)Li NMR spin-lattice (T(1)) and spin-spin (T(2)) 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 (31)P 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.
利用锂-7核磁共振自旋晶格（T(1)）和自旋-自旋（T(2)）弛豫测量技术，研究了锂（Li(+)）在人神经母细胞瘤SH-SY 5 Y细胞亚细胞组分中的结合情况，因为T(1)/T(2)比值是Li(+)结合的一个敏感参数。Li(+)结合常数以及T(1)/T(2)比值表明，大部分Li(+)结合发生在质膜、微粒体和核膜组分中，这些比值远高于在胞质溶胶、细胞核和线粒体中观察到的比值。我们还通过磷-31核磁共振光谱法研究了4 - 6周的慢性Li(+)处理对质膜和细胞匀浆磷脂组成的影响，发现两个组分中磷脂酰肌醇和磷脂酰丝氨酸的水平分别显著升高和降低。基于这些观察结果，我们提出Li(+)主要结合于膜结构域，并且慢性Li(+)处理会改变这些膜位点的磷脂组成。这些发现支持了临床研究的结果，即对双相情感障碍患者进行Li(+)治疗会导致Li(+)结合和磷脂代谢异常。我们还讨论了这些观察结果对Li(+)作用的假定机制的影响，包括细胞膜异常、肌醇耗竭和G蛋白假说。
