Expression of ABCG1, but not ABCA1, correlates with cholesterol release by cerebellar astroglia
Expression of ABCG1, but not ABCA1, correlates with cholesterol release by cerebellar astroglia
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DOI：
10.1074/jbc.m508915200
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发表时间：
2006-02-17
影响因子：
4.8
通讯作者：
Vance, JE
中科院分区：
文献类型：
--
作者：
Karten, B;Campenot, RB;Vance, JE
中枢神经系统脂蛋白介导细胞间胆固醇的交换，并支持突触发生和神经元生长。脑中脂蛋白的主要来源是星形胶质细胞，其合成并分泌高密度脂蛋白样颗粒中的载脂蛋白（apo）E。来自外周循环的少量apoA 1也存在于大脑中。除了从星形胶质细胞直接分泌含apoE的脂蛋白外，胶质细胞衍生的脂蛋白被认为是通过胆固醇经由ATP结合盒（ABC）转运蛋白流出到细胞外载脂蛋白而形成的。我们使用培养的小脑小鼠星形胶质细胞，研究胆固醇的可用性，载脂蛋白E的分泌，ABCA 1和ABCG 1的表达，和胆固醇流出之间的关系。在许多细胞类型中，胆固醇含量、ABCA 1表达和胆固醇流出密切相关。相反，胆固醇富集的胶质细胞未能增加ABCA 1的表达，但ABCG 1的表达和胆固醇流出apoA 1的增加。此外，肝脏X受体（LXR）激动剂TO 901317上调ABCA 1和ABCG 1在神经胶质细胞中的表达，而不刺激胆固醇流出。当胶质细胞富含胆固醇时，产生较大的脂蛋白，而用LXR激动剂处理产生较小的颗粒，当胶质细胞负载胆固醇时，这些颗粒被消除。我们还使用来自ApoE（-/-）小鼠的胶质细胞来区分直接脂蛋白分泌和脂蛋白的细胞外生成。我们的观察表明，部分脂化的载脂蛋白E，直接由神经胶质细胞分泌，很可能是主要的细胞外受体的胆固醇释放从神经胶质细胞的过程中介导的ABCG 1。
Central nervous system lipoproteins mediate the exchange of cholesterol between cells and support synaptogenesis and neuronal growth. The primary source of lipoproteins in the brain is astroglia cells that synthesize and secrete apolipoprotein (apo) E in high density lipoprotein-like particles. Small quantities of apoA1, derived from the peripheral circulation, are also present in the brain. In addition to the direct secretion of apoE-containing lipoproteins from astroglia, glia-derived lipoproteins are thought to be formed by cholesterol efflux to extracellular apolipoproteins via ATP-binding cassette (ABC) transporters. We used cultured cerebellar murine astroglia to investigate the relationship among cholesterol availability, apoE secretion, expression of ABCA1 and ABCG1, and cholesterol efflux. In many cell types, cholesterol content, ABCA1 expression, and cholesterol efflux are closely correlated. In contrast, cholesterol enrichment of glia failed to increase ABCA1 expression, although ABCG1 expression and cholesterol efflux to apoA1 were increased. Moreover, the liver X receptor (LXR) agonist TO901317 up-regulated ABCA1 and ABCG1 expression in glia without stimulating cholesterol efflux. Larger lipoproteins were generated when glia were enriched with cholesterol, whereas treatment with the LXR agonist produced smaller particles that were eliminated when the glia were loaded with cholesterol. We also used glia from ApoE(-/-) mice to distinguish between direct lipoprotein secretion and the extracellular generation of lipoproteins. Our observations indicate that partially lipidated apoE, secreted directly by glia, is likely to be the major extracellular acceptor of cholesterol released from glia in a process mediated by ABCG1.