Srivastava Neelam, Averna Maurizio, Srivastava Rai Ajit K
Clonegen Biotechnology, USA.
Indian J Biochem Biophys. 2008 Dec;45(6):410-5.
Apolipoprotein (apo) E plays an important role in the whole body cholesterol homeostasis. Recent studies suggest that it may also be involved in the local cholesterol transport in the brain, and influence the pathogenesis of Alzheimer's disease (AD) by interacting with the beta-amyloid protein and brain lipoprotein receptors. Since apoE expression is highest in the brain, next only to the liver and associated with the pathogenesis of AD, we hypothesized that dietary and hormonal intervention, known to regulate hepatic apoE expression may also regulate brain apoE and thereby influence local cholesterol transport. To test this hypothesis, groups of male C57BL mice were fed either regular rodent chow or high fat (HF) and high cholesterol enriched diet for 3 weeks. In a separate study, groups of male mice were administered pharmacological doses of 17-beta estradiol for 5 consecutive days and sacrificed on the 6th day. As expected, HF diet elevated liver apoE mRNA and apoE synthesis. Similar to liver, brain apoE mRNA and synthesis also increased, following HF feeding. Estradiol administration increased liver apoE synthesis without affecting apoE mRNA. Interestingly, estradiol administration also increased the brain apoE synthesis, but without altering the brain apoE mRNA. These studies suggested that dietary cholesterol and estrogen administration elevated the brain apoE by different mechanisms.
载脂蛋白（apo）E在全身胆固醇稳态中发挥着重要作用。最近的研究表明，它可能还参与大脑中的局部胆固醇转运，并通过与β-淀粉样蛋白和脑脂蛋白受体相互作用来影响阿尔茨海默病（AD）的发病机制。由于apoE在大脑中的表达仅次于肝脏且最高，并且与AD的发病机制相关，我们推测已知可调节肝脏apoE表达的饮食和激素干预也可能调节脑apoE，从而影响局部胆固醇转运。为了验证这一假设，将雄性C57BL小鼠分组，分别喂食常规啮齿动物饲料或高脂肪（HF）和高胆固醇饮食3周。在另一项研究中，给雄性小鼠连续5天给予药理剂量的17-β雌二醇，并在第6天处死。正如预期的那样，HF饮食升高了肝脏apoE mRNA和apoE合成。与肝脏相似，喂食HF后，脑apoE mRNA和合成也增加。给予雌二醇增加了肝脏apoE合成，但不影响apoE mRNA。有趣的是，给予雌二醇也增加了脑apoE合成，但未改变脑apoE mRNA。这些研究表明，饮食胆固醇和雌激素给药通过不同机制升高脑apoE。
