Soares J C, Chen G, Dippold C S, Wells K F, Frank E, Kupfer D J, Manji H K, Mallinger A G
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.soares+@pitt.edu
Psychiatry Res. 2000 Aug 21;95(2):109-18. doi: 10.1016/s0165-1781(00)00175-x.
This study examined the hypothesis that lithium inhibits the PI signaling pathway in humans during in vivo administration by concurrently measuring PKC isozymes and platelet membrane phosphoinositides in lithium-treated patients and healthy individuals. The platelet membrane and cytosolic levels of PKC alpha, beta I, beta II, delta, and epsilon were measured using Western blotting. The relative platelet membrane contents of phosphatidylinositol (PI), phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP(2)) were measured with two-dimensional thin-layer chromatography. Nine euthymic lithium-treated bipolar subjects and 11 healthy control subjects were studied. Compared to control subjects, lithium-treated bipolar patients had significantly lower levels of cytosolic PKC alpha isozyme (t-test=-3.24, d.f.=17, P=0.01) and PIP(2) platelet membrane levels (t-test=-2.51, d.f.=18, P=0.02), and a trend toward reduced levels of cytosolic PKC beta II isozyme (t=-2.17, d.f.=17, P=0.05). There was no significant correlation between PIP(2) and any of the PKC isozymes. These preliminary findings suggest that chronic lithium treatment may decrease the levels of both cytosolic PKC alpha isozyme and membrane PIP(2) in platelets of bipolar disorder patients.
本研究通过同时测量锂治疗患者和健康个体的蛋白激酶C（PKC）同工酶及血小板膜磷酸肌醇，检验了锂在体内给药期间抑制人类PI信号通路的假设。采用蛋白质印迹法测量血小板膜和胞质中PKCα、βI、βII、δ和ε的水平。用二维薄层色谱法测量磷脂酰肌醇（PI）、磷脂酰肌醇-4-磷酸（PIP）和磷脂酰肌醇-4,5-二磷酸（PIP₂）的相对血小板膜含量。研究了9名处于心境正常期的锂治疗双相情感障碍患者和11名健康对照者。与对照者相比，锂治疗的双相情感障碍患者胞质PKCα同工酶水平显著降低（t检验=-3.24，自由度=17，P=0.01），血小板膜PIP₂水平降低（t检验=-2.51，自由度=18，P=0.02），胞质PKCβII同工酶水平有降低趋势（t=-2.17，自由度=17，P=0.05）。PIP₂与任何PKC同工酶之间均无显著相关性。这些初步研究结果表明，慢性锂治疗可能会降低双相情感障碍患者血小板中胞质PKCα同工酶和膜PIP₂的水平。
