Lithium inhibitable enzymes in postmortem brain of bipolar patients
Lithium inhibitable enzymes in postmortem brain of bipolar patients
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DOI：
10.1016/s0022-3956(03)00044-x
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发表时间：
2003-09-01
影响因子：
4.8
通讯作者：
Belmaker, RH
中科院分区：
文献类型：
--
作者：
Agam, G;Shatiel, G;Belmaker, RH
尽管在流行病学、遗传学和分子水平上进行了大量的努力，但双相情感障碍的病因尚未阐明。为了研究这种疾病的病理生理学可能的贡献成分，我们假设患者脑中治疗相关锂离子浓度抑制的酶水平可能与正常对照不同，并且可能参与疾病的病因学。三个锂代谢酶进行了研究，在死后的双相情感障碍患者和正常对照组的大脑样本。两种酶的表达和功能，显然是参与信号级联反应，IMP酶，参与磷脂酰肌醇循环的第二信使系统，和GSK-3，一系列信号级联反应的介质，没有发现死后的双相患者和9名正常对照额叶和枕叶皮层不同。与正常对照组相比，双相情感障碍患者额叶皮质中只有PAP磷酸酶蛋白水平显著降低，而其mRNA水平和酶活性无显著变化。(C)2003 Elsevier Ltd.保留所有权利。
Despite considerable ongoing efforts at the epidemiological, genetic and molecular level, the etiology of bipolar disorder had not yet been elucidated. To study possible contributing components to the pathophysiology of this disorder, we have hypothesized that levels of enzymes inhibited by therapeutically relevent lithium ion concentrations in the brain of patients may differ from those in normal controls and may be involved in the etiology of the disorder. Three Li-inhibitable enzymes were studied in postmortem brain samples of bipolar patients and normal controls. The expression and function of the two enzymes that are obviously involved in signaling cascades, IMPase, involved in the second messenger system of the phosphatidylinositol cycle, and GSK-3, a mediator of an array of signaling cascades, were not found to be different in postmortem frontal and occipital cortex of bipolar patients and 9 normal controls. Only PAP phosphatase protein levels, but not its mRNA levels or enzymatic activity, were foudn to be significantly decreased in frontal cortex of bipolar patients compared with normal controls. (C) 2003 Elsevier Ltd. All rights reserved.