生物谷報(bào)道：自殺是常見死亡原因之一，美國僅2004年就有32400人死于自殺,，使自殺成為一個(gè)嚴(yán)肅的社會(huì)話題,。排除社會(huì)和心理問題，研究人員認(rèn)為自殺,、抑郁和大腦的血清素(Serotonin)水平下降有關(guān),。盡管尋找負(fù)責(zé)這個(gè)不確定原因的基因的實(shí)驗(yàn)獲得了一些進(jìn)展，但仍有其它基因需要確定,。
德國研究人員決定研究與自殺有關(guān)的蛋白,。Brigitta Bondy與來自慕尼黑Ludwig Maximilians大學(xué)和Max Planck研究所的同事認(rèn)為，蛋白組的變化比基因組的變化更容易識(shí)別,。因此他們嘗試用蛋白組學(xué)技術(shù)分析17位死于自殺的尸體和9位對(duì)照組尸體的腦組織的蛋白表達(dá)情況,。
組織采自前額葉皮層的右半部分，內(nèi)參區(qū)域采自右小腦半球,。平均尸檢間隔時(shí)間,，自殺組為死后18.4±10小時(shí)，對(duì)照組為死亡后9.2?±5.5小時(shí),。Bondy等從一致性樣本中提取蛋白,，進(jìn)行雙向凝膠電泳和銀染，然后切下凝膠中的可能蛋白點(diǎn),，進(jìn)行胰酶消化和基質(zhì)輔助激光解吸離子化質(zhì)譜（matrix-assisted laser desorption/ionisation mass spectrometry ,，MALDI MS）。
結(jié)果顯示,，自殺組和對(duì)照組的小腦組織與預(yù)期一樣沒有不同,，但前額葉皮層有6個(gè)蛋白點(diǎn)明顯不同，其中三個(gè)點(diǎn)只在自殺組存在,，但在對(duì)照組沒有痕跡,。第一個(gè)是膠質(zhì)纖維酸性蛋白（Glial fibrillary acid protein，GFAP）。GFAP與神經(jīng)元功能調(diào)節(jié)和生存有關(guān),，之前有研究認(rèn)為與神經(jīng)退行性疾病有關(guān),。Bondy等檢測(cè)GFAP的兩種異構(gòu)體（其中一種是磷酸化的形式），結(jié)果發(fā)現(xiàn)前額葉皮層中高度磷酸化狀態(tài)的GFAP可能是病理學(xué)自殺原因之一,。
第二種蛋白是錳超氧化物岐化酶（manganese superoxide dismutase）,，一種抗氧化酶，通過清理自由基抵抗氧化壓力,，與精神分裂癥和躁郁癥有關(guān),。
第三種蛋白是alpha-Crystallin chain B，一種小型熱休克蛋白,，某些科學(xué)家認(rèn)為其對(duì)延長(zhǎng)的神經(jīng)性應(yīng)激的毒性效果有反應(yīng),。
研究人員推測(cè)這三個(gè)蛋白點(diǎn)的出現(xiàn)將神經(jīng)生物學(xué)途徑與自殺行為聯(lián)系起來，可能是通過血清素系統(tǒng),。這與之前公布的在大鼠研究中獲得的結(jié)果一致,，但具體機(jī)制仍不清楚,。此次實(shí)驗(yàn)還證明蛋白組學(xué)是研究自殺,、抑郁癥遺傳因素的有力工具。
原始出處:
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.
