Li Xiang, Becker Katrin Anne, Zhang Yang
Department of Molecular Biology, University of Duisburg-Essen, Essen, Germany.
Cell Physiol Biochem. 2010;26(1):41-8. doi: 10.1159/000315104. Epub 2010 May 18.
Lipid rafts are distinct cell membrane microdomains that consist of cholesterol, sphingolipids, and some associated proteins. Accumulating evidence suggests that activation of sphingomyelinase and generation of ceramide mediates clustering of lipid rafts to form large ceramide-enriched platforms, in which transmembrane signals are transmitted or amplified. Ceramide and reactive oxygen species (ROS) are involved in the modulation of the cell membrane and intracellular ion channels, cell proliferation and apoptotic cell death, neutrophil adhesion to the vessel wall, and vascular tone and in the development of cardiovascular diseases to name some important examples. Ceramide triggers the generation of ROS and increases oxidative stress in many mammalian cells and animal models. Moreover, inhibition of ROS generating enzymes or treatment of antioxidants impairs sphingomyelinase activation and ceramide production. Thus, a new concept has been proposed that ceramide-enriched raft platforms are important redox signaling platforms that amplify activation of ROS generating enzymes (e.g. NADPH oxidase family enzymes) and sphingomyelinases. The general function of ceramide to form redox signaling platforms amplifying oxdative stress might be critically involved in the dysfunction of vascular cells induced by death receptor ligands and stress stimuli contributing to the development of cardiovascular diseases.
脂筏是由胆固醇、鞘脂和一些相关蛋白质组成的独特细胞膜微区。越来越多的证据表明，鞘磷脂酶的激活和神经酰胺的生成介导脂筏聚集形成富含神经酰胺的大平台，跨膜信号在其中传递或放大。神经酰胺和活性氧（ROS）参与细胞膜和细胞内离子通道的调节、细胞增殖和凋亡性细胞死亡、中性粒细胞与血管壁的黏附以及血管张力，并在心血管疾病的发生发展中发挥作用，仅举几个重要例子。在许多哺乳动物细胞和动物模型中，神经酰胺会引发ROS的产生并增加氧化应激。此外，抑制ROS生成酶或使用抗氧化剂进行处理会损害鞘磷脂酶的激活和神经酰胺的产生。因此，有人提出了一个新的概念，即富含神经酰胺的筏平台是重要的氧化还原信号平台，可放大ROS生成酶（如NADPH氧化酶家族酶）和鞘磷脂酶的激活。神经酰胺形成放大氧化应激的氧化还原信号平台的一般功能，可能在死亡受体配体和应激刺激诱导的血管细胞功能障碍中起关键作用，而这种功能障碍会促进心血管疾病的发展。
