Altered expression and phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) in postmortem brain of suicide victims with or without depression.
Altered expression and phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) in postmortem brain of suicide victims with or without depression.
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DOI：
10.1016/s0022-3956(03)00047-5
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发表时间：
2003-09
影响因子：
4.8
通讯作者：
G. Pandey;Yogesh K. Dwivedi;Xinguo Ren;H. Rizavi;R. Roberts;R. Conley;C. Tamminga
中科院分区：
文献类型：
--
作者：
G. Pandey;Yogesh K. Dwivedi;Xinguo Ren;H. Rizavi;R. Roberts;R. Conley;C. Tamminga
肉豆蔻酰化富含丙氨酸的 C 激酶底物 (MARCKS) 是一种酸性、热稳定蛋白，参与神经递质释放和再摄取等重要生理功能。它也是蛋白激酶 C (PKC) 磷酸化的底物，并已被证明在情绪障碍的病理生理学中发挥作用。在这项研究中，测定了自杀受害者（有或没有抑郁症）和正常对照受试者死后大脑的前额皮质（PFC）和海马中 MARCKS 的蛋白和 mRNA 表达以及 MARCKS 的磷酸化。自杀受试者和对照组之间的 MARCKS mRNA 和蛋白水平没有显着差异。然而，与正常对照相比，从抑郁自杀受试者获得的 PFC 和海马膜中的 MARCKS 蛋白水平显着增加，但在细胞质部分中则没有显着增加。当测定 PKC 介导的 MARCKS 磷酸化时，观察到与对照人群相比，从完全自杀受试者以及抑郁和非抑郁自杀受试者获得的 PFC 和海马的膜部分中，MARCKS 磷酸化显着降低。尽管抑郁症和非抑郁症自杀受试者中 MARCKS 发生这种改变的机制尚不清楚，但本研究的结果表明，膜 MARCKS 的增加与抑郁症自杀受害者有关，而 MARCKS 磷酸化的减少可能是独立于诊断的自杀受害者的共同特征。
Myristoylated alanine-rich C kinase substrate (MARCKS), an acidic, heat-stable protein, is involved in important physiological functions such as neurotransmitter release and re-uptake. It is also a substrate for phosphorylation by protein kinase C (PKC) and has been shown to play a role in the pathophysiology of mood disorders. In this study, protein and mRNA expression of MARCKS as well as phosphorylation of MARCKS were determined in the prefrontal cortex (PFC) and hippocampus of postmortem brain obtained from suicide victims, with or without depression, and normal control subjects. There were no significant differences in mRNA and protein levels of MARCKS between suicide subjects and controls. However, protein levels of MARCKS were significantly increased in the membrane but not in cytosol fraction of PFC and hippocampus obtained from depressed suicide subjects as compared to normal controls. When PKC-mediated MARCKS phosphorylation was determined, it was observed that MARCKS phosphorylation was significantly decreased in the membrane fraction of PFC and hippocampus obtained from total suicide subjects as well as depressed and non-depressed suicide subjects compared with control population. Although the mechanism of such alterations in MARCKS in depressed and non-depressed suicide subjects is not clear, results of the present study indicate that an increase in membrane MARCKS is associated with depressed suicide victims and a decrease in MARCKS phosphorylation may be a common feature of suicide victims independent of diagnosis.