Identification of Li+ binding sites and the effect of Li+ treatment on phospholipid composition in human neuroblastoma cells:: A 7Li and 31P NMR study

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1741

Article

Layden, BT ; Abukhdeir, AM ; Malarkey, C ; Oriti, LA ; Salah, W ; Stigler, C ; Geraldes, CFGC ; de Freitas, DM

关键词: cell membrane;    cytosol;    lithium;    mitochondria;    NMR;    phospholipid;   

DOI  :  10.1016/j.bbadis.2005.07.004

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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