The pro-apoptotic ARTS/Sept4 protein is significantly reduced in post-mortem brains from schizophrenic patients
The pro-apoptotic ARTS/Sept4 protein is significantly reduced in post-mortem brains from schizophrenic patients
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DOI：
10.1016/j.schres.2007.05.031
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发表时间：
2007-11-01
影响因子：
4.5
通讯作者：
Larisch, Sarit
中科院分区：
文献类型：
--
作者：
Gottfried, Yossi;Rotem, Asaf;Larisch, Sarit
与正常脑相比，精神分裂症脑在大小、体积和结构上表现出各种神经病理学变化。这些结构异常可能是凋亡性细胞死亡的结果。ARTS/Sept 4蛋白在诱导和促进细胞凋亡中起重要作用。虽然ARTS在健康人脑中高度表达，但大多数被检测的精神分裂症脑样品显示ARTS蛋白不表达。具体地说，使用单克隆抗ARTS抗体的蛋白质印迹分析，我们发现，只有1/14的精神分裂症样本（7%）显示出较强的ARTS信号相比，10/15（66.6%）发现在正常对照组。免疫组化检测仅占33.3%（5/15）与对照组相比，精神分裂症患者样本（SE +/- 12.5）显示出任何ARTS免疫反应性双相情感障碍组（13/15）87%（SE +/- 9），抑郁症组（11/14）78%（SE +/- 11.3），正常对照组（10/14）71%（SE +/- 12.5）。在这些精神分裂症样品中测得的细胞凋亡率比在所有其他样品中发现的平均细胞凋亡率降低了四倍。这些数据支持ARTS表达的丧失和对细胞凋亡的敏感性丧失之间的联系。有趣的是，与女性精神分裂症患者和所有其他对照组的男性相比，男性精神分裂症患者的ARTS水平显著较低。我们认为，ARTS可能在精神分裂症的发病机制中起重要作用，并可作为精神分裂症的一个标志物。(c)2007 Elsevier B.V保留所有权利。
Schizophrenic brains exhibit various neuro-pathological changes in size, volume and structure as compared to normal brains. These structural abnormalities could be the result of apoptotic cell death. ARTS/Sept4 protein plays an important role in induction and promotion of apoptosis. Though ARTS is highly expressed in the healthy human brain, most of tested schizophrenic brain samples showed no expression of ARTS protein. Specifically, using Western blot analysis with monoclonal anti-ARTS antibody we found that only I out of 14 schizophrenic samples (7%) showed a strong ARTS signal as compared to 10 out of 15 (66.6%) found in the normal controls group. Furthermore, using immunohistochemistry assay only 33.3% (5 of 15) (SE +/- 12.5) of the schizophrenic patients samples showed any ARTS immunoreactivity as compared to (13 of 15) 87% (SE +/- 9) of bipolar, (11 of 14) 78% (SE +/- 11.3) of major depression and (10 of 14) 71% (SE +/- 12.5) of normal controls. A four-fold reduction in apoptosis rate was measured in these schizophrenic samples as compared to average apoptosis rate found in all other samples. These data support the linkage between loss of ARTS expression and the loss of sensitivity towards apoptosis. Interestingly, levels of ARTS were significantly lower in male schizophrenic patients as compared to female schizophrenic patients, and males of all other control groups. We propose that ARTS may play an important role in the pathogenesis of schizophrenia and could be used as a marker for this disease. (c) 2007 Elsevier B.V All rights reserved.