Expression and regulation of apolipoprotein E receptors in the cells of the central nervous system in culture: A review
Expression and regulation of apolipoprotein E receptors in the cells of the central nervous system in culture: A review
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DOI：
10.1007/s11357-001-0001-9
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发表时间：
2001-01-01
期刊：
影响因子：
--
通讯作者：
Michikawa, M
中科院分区：
文献类型：
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作者：
Fan, QW;Iosbe, I;Michikawa, M
载脂蛋白E(ApoE)在中枢神经系统(CNS)中的重要性日益明显，自从发现apoE epsilon4等位基因是阿尔茨海默病的主要危险因素以来，apoE是主要的载脂蛋白之一，通过apoE受体作为细胞摄取脂蛋白的配体，在中枢神经系统中属于低密度脂蛋白受体(LDLR)家族。最近，LDLR家族被证明具有新的功能，调节细胞内信号，影响神经元和神经胶质功能，存活和再生。然而，载脂蛋白E受体在中枢神经系统中的表达模式尚不完全清楚，已知的是LDLR、极低密度脂蛋白受体(VLDLR)、LDLR相关蛋白(LRP)和载脂蛋白E受体2(ApoER2)结合并内化含apoE的脂蛋白。在这里，我们总结了载脂蛋白E受体在中枢神经系统中的表达，并利用原位杂交和RT-PCR证明了我们关于这些受体在中枢神经系统中的细胞类型特异性表达和调控的额外原始数据。我们使用的细胞是从大鼠脑内分离的神经元、星形胶质细胞、小胶质细胞和少突胶质细胞的高度浓缩培养物和神经母细胞瘤细胞株Neuro2a，这四种受体在神经元、星形胶质细胞、小胶质细胞和少突胶质细胞中都有表达，而LDLR和LRP在Neuro2a细胞中都有表达，我们进一步研究了这些受体的表达通过改变细胞的胆固醇含量来调节，发现在神经元和星形胶质细胞中，只有LDLR在脂蛋白胆固醇内化后表达下调，而在胆固醇剥夺后表达上调，这些数据与以前的研究一起表明，LDLR、VLDL、LRP和LRP在神经元和星形胶质细胞中的表达ApoER2可能参与了载脂蛋白E介导的中枢神经系统细胞，即神经元、星形胶质细胞、小胶质细胞和少突胶质细胞的脂质摄取和/或细胞内信号传递。
The importance of apolipoprotein E (apoE) in the central nervous system (CNS) became increasingly clear since the discovery that apoE epsilon4 allele is a major risk factor for Alzheimer's disease, ApoE is one of the major apolipoproteins that acts as a ligand for the cellular uptake of lipoproteins via apoE receptors, members of low-density lipoprotein receptor (LDLR) family, in the CNS. Recently, LDLR family has been shown to have new functions that modulate intracellular signalling and affect neuronal and glial functions, survival and regeneration. However, the pattern of expression of apoE receptors in the CNS has not been fully clarified yet, The LDLR, very low density lipoprotein receptor(VLDLR), LDLR-related protein (LRP), and apolipoprotein E receptor 2 (apoER2) are known to bind to and internalize apoE-containing lipoproteins. Here we summarize the expression of apoE receptors in the CNS and demonstrate additional our original data on cell type specific expression and regulation of those receptors in the CNS, using in situ hybridization and RT-PCR. The cells used in our study were highly enriched cultures of neurons, astrocytes, microglia and oligodendrocytes isolated from rat brain and neuroblastoma cell line, Neuro2a, All of these four types of receptors were shown to be expressed in neurons, astrocytes, microglia and oligodendrocytes, while LDLR and LRP were expressed in Neuro2a cells, We further examined the regulation of the expression of these receptors by altering the cholesterol content of the cells, and found that only the LDLR expression was downregulated following internalization of lipoprotein cholesterol and upregulated by cholesterol deprivation, in neuronal and astroglial cells, These data together with previous studies suggest that LDLR, VLDL, LRP, and apoER2 may be involved in apoE-mediated lipid uptake and/or intracellular signalling in the cells of the CNS cells, i.e., neurons, astrocytes, microglia, and oligodendrocytes.