Novel role for apolipoprotein E in the central nervous system - Modulation of sulfatide content
Novel role for apolipoprotein E in the central nervous system - Modulation of sulfatide content
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DOI：
10.1074/jbc.m212340200
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发表时间：
2003-03-07
影响因子：
4.8
通讯作者：
Holtzman, DM
中科院分区：
文献类型：
--
作者：
Han, XL;Cheng, H;Holtzman, DM
长期以来，人们一直认为载脂蛋白E（apoE）可能在大脑的脂质代谢中发挥作用。然而，缺乏apoE发挥这种作用的直接证据。我们研究了apoE亚型是否影响脑中的脂质含量。我们比较了野生型小鼠与apoE基因敲除（-/-）和人apoE 3和apoE 4转基因小鼠的大脑，并比较了具有不同apoE亚型的人的脑脊液（CSF）。我们发现apoE对多种磷脂、鞘脂和胆固醇的含量没有影响。然而，apoE对脑和CSF中的硫苷脂（ST）含量有显著影响。发现apoE基因敲除小鼠海马和皮质中的硫苷脂质量比12个月龄的野生型小鼠高61和114 mol%。相反，表达apoE 4的小鼠脑组织中的硫苷脂含量比同龄野生型小鼠低60%。人CSF中ST质量显著依赖于受试者的APOE基因型。对人CSF中潜在的硫苷脂载体的检查表明，硫苷脂与含apoE的高密度脂蛋白特异性相关，表明中枢神经系统（CNS）中的硫苷脂水平可能直接受到调节含apoE的CNS脂蛋白水平的相同代谢途径的调节。apoE在中枢神经系统中的这种新作用可能为apoE与阿尔茨海默病和脑损伤后恢复不良的联系提供新的见解。
It has long been postulated that apolipoprotein E (apoE) may play a role in lipid metabolism in the brain. However, direct evidence that apoE plays such a role is lacking. We investigated whether apoE isoforms influence lipid content in the brain. We compared the brains of wild-type mice to apoE knockout (-/-) and human apoE3 and apoE4 transgenic mice and compared cerebrospinal fluid (CSF) of humans with different apoE isoforms. We found that there was no effect of apoE on the content of multiple phospholipids, sphingolipids, and cholesterol. There was, however, a marked effect of apoE on the sulfatide (ST) content in both the brain and CSF. The sulfatide mass in hippocampus and cortex of apoE knockout mice was found to be 61 and 114 mol% higher than wild-type mice counterparts at 12 months of age. In contrast, the sulfatide content in brain tissues from human apoE4-expressing mice was similar to60% less than those found in wild-type mice of the same age. The ST mass in human CSF was significantly dependent on the APOE genotypes of the subjects. Examination of potential sulfatide carrier(s) in human CSF demonstrated that sulfatides are specifically associated with apoE-containing high density lipoproteins, suggesting that sulfatide levels in the central nervous system (CNS) are likely to be directly modulated by the same metabolic pathways that regulate levels of apoE-containing CNS lipoproteins. This novel role for apoE in the CNS may provide new insights into the connection of apoE with Alzheimer's disease and poor recovery after brain injury.