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Ceramide in Redox Signaling and Cardiovascular Diseases

机译：神经酰胺在氧化还原信号和心血管疾病中的作用

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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.
机译：脂质筏是由胆固醇，鞘脂和一些相关蛋白组成的独特的细胞膜微区。越来越多的证据表明，鞘磷脂酶的激活和神经酰胺的产生介导了脂质筏的聚集，从而形成了富含神经酰胺的大平台，在该平台中跨膜信号得以传输或放大。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，嗜中性白细胞粘附于血管壁，血管张力以及心血管疾病的发展例子。神经酰胺在许多哺乳动物细胞和动物模型中触发ROS的产生并增加氧化应激。此外，抑制产生ROS的酶或抗氧化剂的治疗损害鞘磷脂酶的活化和神经酰胺的产生。因此，已经提出了一种新概念，即富含神经酰胺的筏平台是重要的氧化还原信号平台，其放大了ROS产生酶（例如NADPH氧化酶家族酶）和鞘磷脂酶的活化。神经酰胺形成氧化还原信号平台放大氧化应激的一般功能可能与死亡受体配体诱导的血管细胞功能紊乱和应激刺激密切相关，从而促进心血管疾病的发展。

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