MULLEN POST-DOC/TECHNICIAN SUPPORT

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 众所周知，大豆可以降低胆固醇水平，这与心血管疾病风险的降低相对应。然而，这种降胆固醇作用的机制以及引起这种作用的大豆成分仍存在争议。还不清楚含有内源性异黄酮的大豆蛋白是否会与含有低异黄酮的大豆蛋白具有相同的效果，而大豆蛋白中含有的异黄酮会回补到蛋白质来源。 我们以前在细胞培养模型中已经证明，异黄酮染料木素和大豆苷元增加了固醇调节元件结合蛋白(SREBPs)的处理，并表达了SREBP调节的基因，如HMG辅酶A还原酶、HMG辅酶A合成酶和低密度脂蛋白受体。这项研究将在体内模型中研究异黄酮类化合物是否导致SREBP加工和SREBP调控基因表达的类似增加。以C57BL/6J小鼠为实验动物，分别饲喂致动脉粥样硬化饲料2天、10天或6周。这些饮食将含有低内源性异黄酮量的大豆蛋白，无论有没有 补充异黄酮类或含有大量内源性异黄酮类的大豆蛋白。动物将被处死，并对它们的血浆和肝组织脂质进行分析。用免疫印迹法检测SREBP-2的加工过程和HMG CoA还原酶的蛋白水平。SREBP调控基因的表达水平也将通过实时定量聚合酶链式反应进行研究。我们假设血浆胆固醇和甘油三酯水平将下降，这将对应于SREBP加工以及SREBP调控的基因表达的增加。然而，我们不知道我们是否会在含有大量内源性异黄酮的大豆蛋白或含有少量异黄酮的大豆蛋白中观察到同样的结果，并将异黄酮补充回蛋白质来源。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Soy is known to lower cholesterol levels and this corresponds to a decrease in cardiovascular disease risk. However, the mechanisms of this hypocholesterolemic effect as well as the components of soy that cause thiseffect are a source of controversy. It is also unknown whether soy protein containing endogenous isoflavones would have the same effect as soy protein containing low isoflavones with isoflavones supplemented back to the protein source. We have previously shown in a cell culture model that the isoflavones, genistein and daidzein, increase the processing of the Sterol Regulatory Element Binding Proteins (SREBPs) and the expression SREBP-regulated genes such as HMG CoA reductase, HMG CoA synthase and the LDL receptor. This study will address whether isoflavones cause a similar increase in SREBP processing and SREBP-regulated gene expression in an in vivo model. We will use the C57BL/6J mouse and feed it an atherogenic diet for either 2 days, 10 days or 6 weeks. The diets will contain soy protein with low endogenous amounts of isoflavones with or without isoflavone supplementation or soy protein with high amounts of endogenous isoflavones. The animals will be sacrificed and their plasma and liver tissue lipids will be analyzed. The processing of SREBP-2 and the protein levels of HMG CoA reductase will be measured by immunoblotting. The expression levels of SREBP regulated genes will also be investigated by quantitative real time PCR. We hypothesize that there will be a decrease in plasma cholesterol and triglyceride levels and that this will correspond to an increase in SREBP processing as well as SREBP-regulated gene expression. However, we do not know if we will observe the same results for soy protein containing high amounts of endogenous isoflavones or soy protein containing low amounts of isoflavones with isoflavones supplemented back to the protein source.