三磷酸腺苷结合匣转运蛋白G1(ABCG1)介导的胆固醇流出机制的相关研究

The ATP-binding cassette transporter G1 （ABCG1）is a member of ATP-binding cassette transporters' superfamily。The ABCG1 is known to be able to protect against atherosclerosis, due to the ABCG1 mediating cholesterol efflux from macrophage cell membrane. Related studies have demonstrated that several cholesterol receptors is able to accept the cholesterol from the cell membrane by ABCG1. There are no specific molecular binding between the acceptors and ABCG1 on the cell membrane during the transportation. Addtionnally, the cholesterol moleculars in the cell membrane are distributed in the lipid rafts,the relatively hydrophobic dense microdomains. In the lipid rafts，the cholesterol are bind with other hydrophobic moleculars tightly. Based on the above results, we assume that the ABCG1's expression on the cell surface make the cholesterol molecules in the lipid rafts to be available by a variety of cholesterol receptors. In the current study, we will use the technics of molecular cloning and visualization study of living cells to confirm this hypothesis: ABCG1 is expressed initially within the lipid rafts when it reaches cell membrane. The ABCG1's expression alters cholesterol and sphingomyelin's distribution on the cell surface; ABCG1's expression accelerates the cholesterol extracellar efflux.This study is helpful for understanding the mechanism of ABCG1-mediated cholesterol extracellular efflux, and the physiological function of ABCG1.

三磷酸腺苷结合匣转运蛋白G1（ABCG1）是ATP结合蛋白超家族的一员。由于ABCG1能够使胆固醇从巨噬细胞表面加速流出，而被认为具有抗动脉粥样硬化的保护作用。相关研究观察到多种胆固醇受体可以接受ABCG1从细胞膜表面输出的胆固醇分子，但是并没有观察到ABCG1与受体的直接结合；细胞膜表面的胆固醇分子主要分布在相对疏水致密的微结构域--脂筏内：在脂筏内胆固醇被紧密结合在疏水分子簇内部。因此我们假设ABCG1的表达使细胞膜表面脂筏内的胆固醇分子从脂筏内部游离出来，使多种胆固醇受体能够获得。因此在当前的研究中，我们将围绕这一假设使用分子克隆和活细胞可视化研究等技术手段证实：ABCG1在初始到达细胞膜表面时，表达脂筏内；ABCG1的表达改变了细胞表面胆固醇和鞘磷脂的分布并加速了胆固醇的流出。这一研究将有助于对ABCG1介导的胆固醇流出机制更深入理解，并有助于进一步了解ABCG1的生理功能