title: Identification of Li(+) binding sites and the effect of Li(+) treatment on phospholipid composition in human neuroblastoma cells: a (7)Li and (31)P NMR study.
abstract: 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.
authors.affiliation: Department of Chemistry, Loyola University Chicago, 6525 North Sheridan Road, Chicago, Illinois 60626, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Layden
authors.forename: Abde M
authors.initials: AM
authors.lastname: Abukhdeir
authors.forename: Christopher
authors.initials: C
authors.lastname: Malarkey
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Oriti
authors.forename: Wajeeh
authors.initials: W
authors.lastname: Salah
authors.forename: Claire
authors.initials: C
authors.lastname: Stigler
authors.forename: Carlos F G C
authors.initials: CF
authors.lastname: Geraldes
authors.forename: Duarte
authors.initials: D
authors.lastname: Mota de Freitas
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D007554:Isotopes; D008094:Lithium / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D010759:Phosphorus Isotopes; D011485:Protein Binding
chemical_list: D007554:Isotopes; D008565:Membrane Proteins; D010743:Phospholipids; D010759:Phosphorus Isotopes; D008094:Lithium