Edison Biotechnology Institute and Department of Chemistry and Biochemistry, Ohio University, Athens, Ohio 45701, USA.
Toxicol Appl Pharmacol. 2012 Mar 15;259(3):311-9. doi: 10.1016/j.taap.2012.01.007. Epub 2012 Jan 24.
Lipid rafts are microdomains of the plasma membrane enriched in cholesterol and sphingolipids, and play an important role in the initiation of many pharmacological agent-induced signaling pathways and toxicological effects. The structure of lipid rafts is dynamic, resulting in an ever-changing content of both lipids and proteins. Cholesterol, as a major component of lipid rafts, is critical for the formation and configuration of lipid raft microdomains, which provide signaling platforms capable of activating both pro-apoptotic and anti-apoptotic signaling pathways. A change of cholesterol level can result in lipid raft disruption and activate or deactivate raft-associated proteins, such as death receptor proteins, protein kinases, and calcium channels. Several anti-cancer drugs are able to suppress growth and induce apoptosis of tumor cells through alteration of lipid raft contents via disrupting lipid raft integrity.
脂质筏是富含胆固醇和鞘脂的质膜微区,在许多药物诱导的信号通路和毒理学效应的起始中发挥重要作用。脂质筏的结构是动态的,导致脂质和蛋白质的含量不断变化。胆固醇作为脂质筏的主要成分,对于脂质筏微区的形成和构型至关重要,它提供了能够激活促凋亡和抗凋亡信号通路的信号平台。胆固醇水平的变化会导致脂质筏的破坏,并激活或失活与脂质筏相关的蛋白质,如死亡受体蛋白、蛋白激酶和钙通道。一些抗癌药物能够通过破坏脂质筏的完整性来改变脂质筏的含量,从而抑制肿瘤细胞的生长并诱导其凋亡。