Svensson M, Sköld K, Nilsson A, Fälth M, Svenningsson P, Andrén P E
Laboratory for Biological and Medical Mass Spectrometry, Uppsala University, Box 583 Biomedical Centre, SE-75123 Uppsala, Sweden.
Biochem Soc Trans. 2007 Jun;35(Pt 3):588-93. doi: 10.1042/BST0350588.
Biological function is mainly carried out by a dynamic population of proteins and peptides which may be used as markers for disease diagnosis, prognosis and as a guide for effective treatment. The study of proteins is called proteomics and it is generally performed by two-dimensional gel electrophoresis and mass spectrometric methods. However, gel-based proteomics is methodologically restricted from the low mass region, which includes important endogenous peptides. The study of endogenous peptides, peptidomics, is complicated by protein fragments produced post-mortem during conventional sample handling. Nanoflow liquid chromatography and MS, together with improved methods for sample preparation, have been used to semi-quantitatively monitor endogenous peptides in brain tissue. When rapidly heat-denatured brain tissue was analysed, these methods enabled simultaneous detection of hundreds of peptides and the identification of several endogenous peptides not previously described in the literature. In an application of the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model for Parkinson's disease, the expression of the small protein PEP-19 was compared with controls. The levels were found to be significantly decreased in the striatum of MPTP-treated animals.
生物功能主要由动态的蛋白质和肽群体来执行，这些蛋白质和肽可用作疾病诊断、预后的标志物以及有效治疗的指导。对蛋白质的研究称为蛋白质组学，通常通过二维凝胶电泳和质谱方法进行。然而，基于凝胶的蛋白质组学在低质量区域存在方法学上的限制，该区域包括重要的内源性肽。对内源性肽的研究，即肽组学，因传统样品处理过程中死后产生的蛋白质片段而变得复杂。纳流液相色谱和质谱，以及改进的样品制备方法，已被用于半定量监测脑组织中的内源性肽。当对快速热变性的脑组织进行分析时，这些方法能够同时检测数百种肽，并鉴定出文献中先前未描述的几种内源性肽。在帕金森病的MPTP（1-甲基-4-苯基-1,2,3,6-四氢吡啶）模型的应用中，将小蛋白PEP-19的表达与对照组进行了比较。发现在MPTP处理动物的纹状体中其水平显著降低。
