Prabakaran Sudhakaran, Wengenroth Martina, Lockstone Helen E, Lilley Kathryn, Leweke F Markus, Bahn Sabine
Institute of Biotechnology and Department of Biochemistry, Cambridge Centre for Proteomics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QT, United Kingdom.
J Proteome Res. 2007 Jan;6(1):141-9. doi: 10.1021/pr060308a.
The molecular disease mechanisms associated with schizophrenia remain largely unknown. Although primarily considered a disorder of the brain, there is evidence of a peripheral component to schizophrenia. In this study, we investigated liver tissue and red blood cells (RBC) from schizophrenia patients and controls using 2-D DIGE proteomic analysis. Fourteen proteins were significantly altered in liver samples from schizophrenia patients (n = 15) compared to healthy controls (n = 15). Analysis of the schizophrenia RBC proteome revealed 8 proteins significantly altered in samples from schizophrenia patients (13 antipsychotic-treated and 7 drug-naïve) compared to controls (n = 20). Six of the altered proteins in the liver and four of the altered RBC proteins are related to oxidative stress. These results corroborate our earlier findings obtained from post-mortem brain studies and substantiate our hypothesis that metabolic alterations leading to oxidative stress are linked to the schizophrenia disease process. Our results also suggest that at least some of the pathological processes associated with the schizophrenia disease process can be traced in peripheral tissue. If peripheral cells can be used as a disease surrogate, promising new investigative avenues could be explored.
与精神分裂症相关的分子疾病机制在很大程度上仍然未知。尽管精神分裂症主要被认为是一种脑部疾病,但有证据表明其存在外周因素。在本研究中,我们使用二维差异凝胶电泳蛋白质组分析方法,对精神分裂症患者和对照组的肝脏组织及红细胞(RBC)进行了研究。与健康对照组(n = 15)相比,精神分裂症患者(n = 15)肝脏样本中有14种蛋白质发生了显著变化。对精神分裂症患者红细胞蛋白质组的分析显示,与对照组(n = 20)相比,精神分裂症患者(13例接受抗精神病药物治疗,7例未接受药物治疗)样本中有8种蛋白质发生了显著变化。肝脏中6种变化的蛋白质和红细胞中4种变化的蛋白质与氧化应激有关。这些结果证实了我们早期从尸检脑研究中获得的发现,并证实了我们的假设,即导致氧化应激的代谢改变与精神分裂症疾病进程相关。我们的结果还表明,与精神分裂症疾病进程相关的至少一些病理过程可以在外周组织中找到踪迹。如果外周细胞可以用作疾病替代物,那么就可以探索出有前景的新研究途径。