THE ROLES OF PROHIBITINS (PHBS) IN 3T3-L1 ADIPOCYTE DIFFERENTIATION

抑制素 (PHBS) 在 3T3-L1 脂肪细胞分化中的作用

• 批准号: 7959162
• 负责人: DONG LIU
• 金额: $ 9.41万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959162
• 关键词: Adipose tissue; Binding Sites; Bioinformatics; Biomedical Research; Computer Retrieval of Information on Scientific Projects Database; Data; Estrogen Receptors; Funding; Goals; Grant; Human; Institution; Mus; Phosphorylation; Proteins; Research; Research Personnel; Resources; Role; Small Interfering RNA; Source; Transgenic Organisms; United States National Institutes of Health; Up-Regulation; adipocyte differentiation; base; lipid biosynthesis; promoter; receptor; transcription factor

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. A. Specific Aims The goal of this proposal is to determine the functional significance of prohibitins during 3T3-L1 adipocyte differentiation. Our preliminary data showed that both of these prohibitins (PHBs), including PHB1 and PHB2 (repressor of estrogen receptor activity, REA), were significantly increased during the adipocyte differentiation of 3T3-L1 preadipocytes. Moreover, 3T3-L1 adipocyte differentiation was impaired after the simultaneous knockdown of either PHBs protein by siRNA-PHB1 or siRNA-REA. So, our first aim is to examine the functional mechanism (phosphorylation and subcellular translocation) of PHBs during adipogenesis. Based on the bioinformatics analyses, we found several putative Egr-1 transcription factor binding sites in the mouse and human PHBs promoters. In addition, we observed that Egr-1 expression was induced prior to the increase of PHBs during 3T3-L1 adipocyte differentiation. Furthermore, the expression of PHBs proteins was upregulated in the adipose tissue in adipose-transgenic Egr-1 mice. Our second aim is to determine that Egr-1 is a critical modulator of PHBs upregulation during 3T3-L1 adipocyte differentiation.

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来源获得了主要资金， 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。 A.具体目标 本提案的目的是确定在3 T3-L1脂肪细胞分化过程中，白藜芦醇苷的功能意义。我们的初步数据表明，这两个阿比丁（PHB），包括PHB 1和PHB 2（雌激素受体活性的阻遏物，REA），在3 T3-L1前脂肪细胞的脂肪细胞分化过程中显着增加。此外，3 T3-L1脂肪细胞分化受损后，同时敲低任一PHBs蛋白的siRNA-PHB 1或siRNA-REA。因此，我们的第一个目标是研究脂肪形成过程中的功能机制（磷酸化和亚细胞易位）。基于生物信息学分析，我们发现了几个推定的Egr-1转录因子结合位点的小鼠和人的PHBs启动子。此外，我们观察到，Egr-1的表达诱导之前，在3 T3-L1脂肪细胞分化过程中的PHBs的增加。此外，脂肪转基因Egr-1小鼠脂肪组织中的PHBs蛋白表达上调。我们的第二个目的是确定Egr-1是3 T3-L1脂肪细胞分化过程中PHBs上调的关键调节剂。