Department of Analytical Chemistry, Medical University of Bialystok, Poland.
Mass Spectrometry Center, QOPNA, Department of Chemistry, University of Aveiro, Portugal.
J Pharm Biomed Anal. 2018 Jun 5;155:185-193. doi: 10.1016/j.jpba.2018.03.068. Epub 2018 Apr 4.
Psoriasis is a chronic, immune-mediated inflammatory skin disease with severe consequences for the whole organism. The lack of complete knowledge of the main factors predisposing an individual to the appearance of psoriatic lesions, has recently led to the search for modifications in biochemical pathways participating in the development of this disease. We therefore aimed to investigate changes in the plasma proteomic profile of patients with psoriasis.
A proteomics approach was used to analyze the expression of proteins in plasma from psoriatic patients and healthy controls (sex- and age-matched individuals). The analysis was performed using gel electrophoresis, followed by nanoflow LC-MS/MS using a Q-Exactive OrbiTrap mass spectrometer.
Proteomic data indicated a significant decrease in the level of proteins involved in lipid metabolism, such as apolipoprotein M, and proteins involved in the management of vitamin D levels in psoriatic patients' plasma. These changes were accompanied by the expression of proteins involved in immune response and signal transduction. This was particularly evident by the level of transcriptional factors, including AT motif binding factor 1, which regulates excessive cellular proliferation and differentiation. It was also suggested that psoriasis development was associated with increased expression of proteins directly involved in signaling molecule secretion [biotinidase and BAI1-associated protein 3]. In addition, the lipid peroxidation product - 4-hydroxynonenal (4-HNE) generates higher level of adducts with proteins in the plasma of psoriatic patients. Moreover, plasma proteins from healthy subjects creating with 4-HNE adducts were mainly characterized as structural, while in the plasma of psoriatic patients, increased levels of 4-HNE-protein adducts with catalytic activity were observed.
The results presented herein confirm the current knowledge about the profile of proteins responsible for the immune response and management of vitamin D in the plasma of psoriatic patients. However, several new proteins were also identified, which are involved in signal transduction and lipid metabolism as well as catalytic activity. The expression or structure of these proteins was shown to change through the course of the development of psoriasis. This knowledge may help contribute to the design of more specific pharmacotherapy.
银屑病是一种慢性、免疫介导的炎症性皮肤病，对整个机体都有严重影响。由于对导致个体出现银屑病损伤的主要因素缺乏全面了解，最近人们开始寻找参与该疾病发展的生化途径的改变。因此，我们旨在研究银屑病患者血浆蛋白质组谱的变化。
采用蛋白质组学方法分析银屑病患者和健康对照者（性别和年龄匹配）血浆中的蛋白质表达。使用凝胶电泳进行分析，然后使用 Q-Exactive OrbiTrap 质谱仪进行纳流 LC-MS/MS 分析。
蛋白质组学数据表明，银屑病患者血浆中参与脂质代谢的蛋白质（如载脂蛋白 M）和参与维生素 D 水平管理的蛋白质水平显著降低。这些变化伴随着参与免疫反应和信号转导的蛋白质的表达。这一点尤其明显，因为转录因子（如调节细胞过度增殖和分化的 AT motif 结合因子 1）的水平升高。此外，还表明银屑病的发展与直接参与信号分子分泌的蛋白质（如生物素酶和 BAI1 相关蛋白 3）的表达增加有关。此外，银屑病患者血浆中的脂质过氧化产物 - 4-羟壬烯醛（4-HNE）与蛋白质形成更高水平的加合物。此外，与 4-HNE 加合物形成的健康受试者血浆蛋白质主要为结构蛋白，而在银屑病患者的血浆中，观察到具有催化活性的 4-HNE-蛋白质加合物的水平增加。
本文的结果证实了目前关于银屑病患者血浆中负责免疫反应和维生素 D 管理的蛋白质谱的知识。然而，还发现了几种新的蛋白质，它们参与信号转导和脂质代谢以及催化活性。这些蛋白质的表达或结构随着银屑病的发展而发生变化。这些知识可能有助于设计更具特异性的药物治疗方法。
