MULLEN POST-DOC/TECHNICIAN SUPPORT

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 众所周知，大豆可以降低胆固醇水平，这相当于降低心血管疾病的风险。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是一个争议的来源。还不知道含有内源性异黄酮的大豆蛋白是否会具有与含有低异黄酮的大豆蛋白相同的效果，其中异黄酮补充回蛋白质来源。 我们先前已经在细胞培养模型中表明，异黄酮、染料木素和大豆苷元增加了甾醇调节元件结合蛋白（SREBP）的加工和SREBP调节基因（如HMG CoA还原酶、HMG CoA合酶和LDL受体）的表达。本研究将探讨在体内模型中，β-胆甾酮是否会导致SREBP加工和SREBP调节基因表达的类似增加。我们将使用C57 BL/6 J小鼠并喂食致动脉粥样硬化饮食2天、10天或6周。饮食将含有大豆蛋白和低内源量的异黄酮， 补充维生素C或含有大量内源性维生素C的大豆蛋白。将处死动物，并分析其血浆和肝组织脂质。将通过免疫印迹法测量SREBP-2的加工和HMG CoA还原酶的蛋白水平。还将通过定量真实的时间PCR研究SREBP调节基因的表达水平。我们假设血浆胆固醇和甘油三酯水平会降低，这将对应于SREBP加工以及SREBP调节基因表达的增加。然而，我们不知道对于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，在将异黄酮补充回蛋白质来源的情况下，我们是否会观察到相同的结果。

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.