生物谷报道：自杀是常见死亡原因之一，美国仅2004年就有32400人死于自杀，使自杀成为一个严肃的社会话题。排除社会和心理问题，研究人员认为自杀、抑郁和大脑的血清素(Serotonin)水平下降有关。尽管寻找负责这个不确定原因的基因的实验获得了一些进展，但仍有其它基因需要确定。
德国研究人员决定研究与自杀有关的蛋白。Brigitta Bondy与来自慕尼黑Ludwig Maximilians大学和Max Planck研究所的同事认为，蛋白组的变化比基因组的变化更容易识别。因此他们尝试用蛋白组学技术分析17位死于自杀的尸体和9位对照组尸体的脑组织的蛋白表达情况。
组织采自前额叶皮层的右半部分，内参区域采自右小脑半球。平均尸检间隔时间，自杀组为死后18.4±10小时，对照组为死亡后9.2?±5.5小时。Bondy等从一致性样本中提取蛋白，进行双向凝胶电泳和银染，然后切下凝胶中的可能蛋白点，进行胰酶消化和基质辅助激光解吸离子化质谱（matrix-assisted laser desorption/ionisation mass spectrometry ，MALDI MS）。
结果显示，自杀组和对照组的小脑组织与预期一样没有不同，但前额叶皮层有6个蛋白点明显不同，其中三个点只在自杀组存在，但在对照组没有痕迹。第一个是胶质纤维酸性蛋白（Glial fibrillary acid protein，GFAP）。GFAP与神经元功能调节和生存有关，之前有研究认为与神经退行性疾病有关。Bondy等检测GFAP的两种异构体（其中一种是磷酸化的形式），结果发现前额叶皮层中高度磷酸化状态的GFAP可能是病理学自杀原因之一。
第二种蛋白是锰超氧化物岐化酶（manganese superoxide dismutase），一种抗氧化酶，通过清理自由基抵抗氧化压力，与精神分裂症和躁郁症有关。
第三种蛋白是alpha-Crystallin chain B，一种小型热休克蛋白，某些科学家认为其对延长的神经性应激的毒性效果有反应。
研究人员推测这三个蛋白点的出现将神经生物学途径与自杀行为联系起来，可能是通过血清素系统。这与之前公布的在大鼠研究中获得的结果一致，但具体机制仍不清楚。此次实验还证明蛋白组学是研究自杀、抑郁症遗传因素的有力工具。
原始出处:
Journal of Psychiatric Research
Volume 41, Issue 6, September 2007, Pages 493-501
Comparative proteomic analysis with postmortem prefrontal cortex tissues of suicide victims versus controls
Katja Schlichta, Andreas Büttnerb, Frank Siedlerc, Bea Schefferc, Peter Zilla, Wolfgang Eisenmengerb, Manfred Ackenheila and Brigitta Bondya, ,
aPsychiatric Hospital of the Ludwig-Maximilians-University, Munich, Nussbaumstrasse 7, D-80336 Munich, Germany
bInstitute for Legal Medicine, Ludwig-Maximilians-University Munich, Frauenlobstrasse 7, D-80337 Munich, Germany
cMax-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany
Received 15 November 2005; revised 8 February 2006; accepted 7 April 2006. Available online 5 June 2006.
Abstract
Background：The origin of suicidal behaviour is multifactorial including genetic, neurobiological and psychosocial correlates. Although there is no doubt that serotonin has a central role, the overall genetic findings with candidate genes of the serotonergic pathway are relatively inconsistent and suggests that other, yet unidentified, genes and gene products are also contributing to the vulnerability of suicidality. Proteomics is a powerful method to investigate modifications in protein expression.
Methods ：We performed comparative proteomic analysis with prefrontal cortex tissues of 17 suicide victims and 9 controls.
Results ：Applying two dimensional gel electrophoresis and image analysis we detected five protein spots to differ significantly in intensities between both groups. Three of them appeared only in suicide victims and could be identified by means of MALDI-TOF-MS analysis and protein database search as α crystallin chain B (CRYAB), glial fibrillary acidic protein (GFAP) and manganese superoxide dismutase (SOD2). CRYAB belongs to the low molecular heat shock proteins and GFAP is known as a marker of astrocytic activation in gliosis. SOD2 is a major antioxidant enzyme protecting cells against oxidative injury. Two further spots revealed higher intensities in the control group but had no unambiguous protein to match.
Conclusions ：Our findings suggest that proteins, being involved in glial function, neurodegeneration and oxidative stress neuronal injury, might also have an impact upon the neurobiological cascade leading to suicidality. As animal data provide evidence for an up-regulation of GFAP synthesis in astrocytes due to alterations in 5-HT levels, similar mechanisms of interaction might also be relevant in humans.
Keywords: Suicide; Proteome; Postmortem; 2D-electrophoresis; Serotonin
Corresponding author. Tel.: +49 89 5160 2741; fax: +49 89 5160 4741.
