自杀者前额叶皮层中的5-脂氧合酶。

Tolga Uz, Yogesh Dwivedi, Ghanshyam N Pandey, Rosalinda C Roberts, Robert R Conley, Radmila Manev, Hari Manev
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引用次数: 9

摘要

5-脂氧合酶(5-LOX)是一种参与白三烯合成的酶,在大脑中表达,并与阿尔茨海默病和抑郁症有关。最近,有人怀疑白三烯受体拮抗剂可能与自杀有关。在这项工作中,我们研究了来自抑郁症自杀受害者和匹配对照的大脑样本中的5-LOX蛋白。我们使用免疫印迹法(Western immunoblotting)检测针对Ser(523)-磷酸化5-LOX (p5-LOX)的抗体,以评估蛋白激酶a介导的5-LOX磷酸化,以及针对5-LOX总蛋白的抗体。在前额叶皮层样品的总匀浆中,5-LOX含量在对照组和自杀组之间没有差异,但p5-LOX在自杀组中显著升高。自杀者细胞膜部分5-LOX蛋白含量降低,细胞质部分5-LOX蛋白含量升高。我们认为,需要对大脑5-LOX进行进一步的研究,以阐明本研究中观察到的蛋白质改变的功能意义,并进一步探索5-LOX在抑郁和自杀中的假设作用。
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5-Lipoxygenase in the Prefrontal Cortex of Suicide Victims.

5-lipoxygenase (5-LOX), an enzyme involved in leukotriene synthesis, is expressed in the brain and has been associated with Alzheimer's disease and depression. Recently, it has been suspected that leukotriene receptor antagonists might be associated with suicide. In this work, we investigated the 5-LOX protein in the brain samples from depressed suicide victims and matching controls. We used Western immunoblotting with an antibody against Ser(523)-phosphorylated 5-LOX (p5-LOX) to evaluate protein kinase A-mediated 5-LOX phosphorylation, and in addition, an antibody against the total 5-LOX protein. In the total homogenate of the prefrontal cortex samples, 5-LOX content did not differ in the control and suicide groups but p5-LOX was significantly elevated in the suicide samples. The 5-LOX protein content was reduced in the membrane fraction and increased in the cytosol fraction of suicide victims. We propose that further studies of brain 5-LOX are needed to elucidate the functional implications of the protein alterations observed in our present study, and to further explore a putative role of 5-LOX in depression and suicide.

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