Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia.
Molecules. 2021 Sep 1;26(17):5311. doi: 10.3390/molecules26175311.
Cannabis use has been growing recently and it is legally consumed in many countries. Cannabis has a variety of phytochemicals including cannabinoids, which might impair the peripheral systems responses affecting inflammatory and immunological pathways. However, the exact signaling pathways that induce these effects need further understanding. The objective of this study is to investigate the serum proteomic profiling in patients diagnosed with cannabis use disorder (CUD) as compared with healthy control subjects. The novelty of our study is to highlight the differentially changes proteins in the serum of CUD patients. Certain proteins can be targeted in the future to attenuate the toxicological effects of cannabis. Blood samples were collected from 20 male individuals: 10 healthy controls and 10 CUD patients. An untargeted proteomic technique employing two-dimensional difference in gel electrophoresis coupled with mass spectrometry was employed in this study to assess the differentially expressed proteins. The proteomic analysis identified a total of 121 proteins that showed significant changes in protein expression between CUD patients (experimental group) and healthy individuals (control group). For instance, the serum expression of inactive tyrosine protein kinase PEAK1 and tumor necrosis factor alpha-induced protein 3 were increased in CUD group. In contrast, the serum expression of transthyretin and serotransferrin were reduced in CUD group. Among these proteins, 55 proteins were significantly upregulated and 66 proteins significantly downregulated in CUD patients as compared with healthy control group. Ingenuity pathway analysis (IPA) found that these differentially expressed proteins are linked to p38MAPK, interleukin 12 complex, nuclear factor-κB, and other signaling pathways. Our work indicates that the differentially expressed serum proteins between CUD and control groups are correlated to liver X receptor/retinoid X receptor (RXR), farnesoid X receptor/RXR activation, and acute phase response signaling.
大麻的使用最近有所增加，在许多国家都合法消费。大麻含有多种植物化学物质，包括大麻素，这些物质可能会损害外周系统的反应，影响炎症和免疫途径。然而，诱导这些效应的确切信号通路仍需要进一步研究。本研究的目的是比较大麻使用障碍（CUD）患者与健康对照者的血清蛋白质组谱。本研究的新颖之处在于强调了 CUD 患者血清中差异变化的蛋白质。某些蛋白质可以作为未来的靶点，以减轻大麻的毒性作用。从 20 名男性个体中采集了血液样本：10 名健康对照者和 10 名 CUD 患者。本研究采用二维差异凝胶电泳结合质谱的非靶向蛋白质组学技术来评估差异表达的蛋白质。蛋白质组学分析共鉴定出 121 种蛋白质，这些蛋白质在 CUD 患者（实验组）和健康个体（对照组）之间的蛋白质表达水平有显著变化。例如，PEAK1 无活性酪氨酸蛋白激酶和肿瘤坏死因子-α诱导蛋白 3 的血清表达在 CUD 组中增加。相反，转甲状腺素和血清转铁蛋白的血清表达在 CUD 组中减少。在这些蛋白质中，与健康对照组相比，CUD 患者中有 55 种蛋白质显著上调，66 种蛋白质显著下调。IPA 分析发现，这些差异表达的蛋白质与 p38MAPK、白细胞介素 12 复合物、核因子-κB 等信号通路有关。我们的工作表明，CUD 组和对照组之间差异表达的血清蛋白与肝 X 受体/视黄醇 X 受体（RXR）、法尼醇 X 受体/RXR 激活和急性期反应信号有关。
