Callera Glaucia E, Montezano Augusto Ci, Yogi Alvaro, Tostes Rita Ca, Touyz Rhian M
Kidney Research Centre, Ottawa Health Research Institute, University of Ottawa, Ottawa, Canada.
Curr Opin Nephrol Hypertens. 2007 Mar;16(2):90-104. doi: 10.1097/MNH.0b013e328040bfbd.
Lipid rafts are emerging as key players in the integration of cellular responses. Alterations in these highly regulated signaling cascades are important in structural, mechanical and functional abnormalities that underlie vascular pathological processes. The present review focuses on recent advances in signal transduction through caveolae/lipid rafts, implicated in hypertensive processes.
Caveolae/lipid rafts function as sites of dynamic regulatory events in receptor-induced signal transduction. Mediators of vascular function, including G-protein coupled receptors, Src family tyrosine kinases, receptor tyrosine kinases, protein phosphatases and nitric oxide synthase, are concentrated within these microdomains. The assembly of functionally active nicotinamide adenine dinucleotide phosphate oxidase and subsequent reactive oxygen species production are also dependent on interactions within the caveolae/lipid rafts. Recent findings have also demonstrated the importance of actin-cytoskeleton and focal adhesion sites for protein interactions with caveolae/lipid raft.
Many vascular signaling processes are altered in hypertension. Whether these events involve lipid rafts/caveolae remains unclear. A better understanding of how signaling molecules compartmentalize in lipid rafts/caveolae will provide further insights into molecular mechanisms underlying vascular damage in cardiovascular disease.
脂筏正逐渐成为细胞反应整合中的关键参与者。这些高度调控的信号级联反应的改变在构成血管病理过程基础的结构、机械和功能异常中起着重要作用。本综述聚焦于通过小窝/脂筏进行的信号转导的最新进展,这些进展与高血压过程有关。
小窝/脂筏在受体诱导的信号转导中作为动态调节事件的位点发挥作用。血管功能的介质,包括G蛋白偶联受体、Src家族酪氨酸激酶、受体酪氨酸激酶、蛋白磷酸酶和一氧化氮合酶,都集中在这些微结构域内。功能活性烟酰胺腺嘌呤二核苷酸磷酸氧化酶的组装以及随后的活性氧生成也依赖于小窝/脂筏内的相互作用。最近的发现还证明了肌动蛋白细胞骨架和粘着斑位点对于蛋白质与小窝/脂筏相互作用的重要性。
许多血管信号转导过程在高血压中会发生改变。这些事件是否涉及脂筏/小窝仍不清楚。更好地理解信号分子如何在脂筏/小窝中进行区室化,将为深入了解心血管疾病中血管损伤的分子机制提供进一步的见解。