Studies on Regulatory Mechanism of Secretion of VLDL

为了预防心脏病，需要建立动脉粥样硬化的治疗方法和预防方法。特别是，基于减少VLDL从肝脏分泌到血液的预防方法被认为对VLDL和LDL高脂血症都有效。基于这些思想，研究了与载脂蛋白B-100的调节降解有关的ER-60。ER-60的活性是通过与内质网凝集素样分子伴侣钙粘蛋白的管腔结构域结合来调节的。为了确定ER-60与Calnexin结合的位置，确定了ER-60的结构域结构。Er-60由a、b、b‘和a’四个结构域组成。在结构域中，b‘是与Calnexin结合所必需的。以往的研究表明，在HepG2细胞中，ER-60可与载脂蛋白B-100和Bip结合。在本研究中，Bip对ER-60的活性有刺激作用。此外，我们还发现，一种大豆7S球蛋白对载脂蛋白100-B的合成具有降低作用，它抑制了ER-60的转录。

Establishment of therapeutics and prevention methods of an atherosclerosis is demanded to prevent a cardiac disease. Especially, the preventing method based on decrease in the VLDL secretion from liver into blood is thought effective in both VLDL- and LDL-hyperlipidemia. Based on these ideas, ER-60, which is concerned to the regulatory degradation of apolipoprotein B-100, was studied. The activity of ER-60 is regulated by a binding with the lumen domain of calnexin, which is a lectin-like molecular chaperone of endoplasmic reticulum. To identify the site of ER-60 for the binding with calnexin, the domain structure of ER-60 was determined. ER-60 was shown to be composed of four domains, a, b, b' and a'. Among domains, b' was essential for the binding with calnexin. In previous study, it has been shown that ER-60 bound to both apolopoprotein B-100 and BiP in HepG2 cell. In this study, BiP was shown to have stimulating effect on the activity of ER-60. In addition, we found that a soy 7S globulin, which has a lowering effect on synthesis of apolipoprotein 100-B, depresses the transcription of ER-60.