Marques-da-Silva Dorinda, Lagoa Ricardo
LSRE-Laboratory of Separation and Reaction Engineering and LCM-Laboratory of Catalysis and Materials, School of Management and Technology, Polytechnic Institute of Leiria, Morro do Lena-Alto do Vieiro, 2411-901 Leiria, Portugal.
ALiCE-Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
Molecules. 2023 Sep 13;28(18):6598. doi: 10.3390/molecules28186598.
The plasma membrane lipid rafts are cholesterol- and sphingolipid-enriched domains that allow regularly distributed, sub-micro-sized structures englobing proteins to compartmentalize cellular processes. These membrane domains can be highly heterogeneous and dynamic, functioning as signal transduction platforms that amplify the local concentrations and signaling of individual components. Moreover, they participate in cell signaling routes that are known to be important targets of environmental toxicants affecting cell redox status and calcium homeostasis, immune regulation, and hormonal functions. In this work, the evidence that plasma membrane raft-like domains operate as hubs for toxicants' cellular actions is discussed, and suggestions for future research are provided. Several studies address the insertion of pesticides and other organic pollutants into membranes, their accumulation in lipid rafts, or lipid rafts' disruption by polychlorinated biphenyls (PCBs), benzo[a]pyrene (B[a]P), and even metals/metalloids. In hepatocytes, macrophages, or neurons, B[a]P, airborne particulate matter, and other toxicants caused rafts' protein and lipid remodeling, oxidative changes, or amyloidogenesis. Different studies investigated the role of the invaginated lipid rafts present in endothelial cells in mediating the vascular inflammatory effects of PCBs. Furthermore, in vitro and in vivo data strongly implicate raft-localized NADPH oxidases, the aryl hydrocarbon receptor, caveolin-1, and protein kinases in the toxic mechanisms of occupational and environmental chemicals.
质膜脂筏是富含胆固醇和鞘脂的结构域，可形成包裹蛋白质的规则分布的亚微米级结构，从而使细胞过程分区化。这些膜结构域高度异质且动态变化，充当信号转导平台，放大单个组分的局部浓度和信号。此外，它们参与细胞信号传导途径，这些途径是影响细胞氧化还原状态、钙稳态、免疫调节和激素功能的环境毒物的重要作用靶点。在这项工作中，讨论了质膜类筏结构域作为毒物细胞作用枢纽的证据，并提供了未来研究的建议。多项研究涉及农药和其他有机污染物插入膜中、它们在脂筏中的积累，或多氯联苯（PCBs）、苯并[a]芘（B[a]P）甚至金属/类金属对脂筏的破坏。在肝细胞、巨噬细胞或神经元中，B[a]P、空气颗粒物和其他毒物导致脂筏的蛋白质和脂质重塑、氧化变化或淀粉样蛋白生成。不同的研究调查了内皮细胞中内陷脂筏在介导PCBs血管炎症效应中的作用。此外，体外和体内数据强烈表明，筏定位的NADPH氧化酶、芳烃受体、小窝蛋白-1和蛋白激酶参与职业和环境化学物质的毒性机制。
