IDENTIFICATION OF THE PHYSIOLOGICALLY RELEVANT ENDOGENOUS LIGAND FOR PPAR?

PPAR 的生理相关内源性配体的鉴定？

• 批准号: 7954028
• 负责人: Manu V. Chakravarthy
• 金额: $ 0.35万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954028
• 关键词: Agonist; Binding; Computer Retrieval of Information on Scientific Projects Database; DNA Binding; Disease; Fatty-acid synthase; Funding; Gene Expression; Generations; Grant; Human; Injection of therapeutic agent; Institution; Ligands; Liver; Mass Spectrum Analysis; Molecular; Mus; Nuclear; Nuclear Receptors; Palmitates; Peroxisome Proliferator-Activated Receptors; Pharmaceutical Preparations; Phospholipids; Research; Research Personnel; Resources; Source; Tissues; United States National Institutes of Health; biomedical resource; lipid metabolism

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. PPAR¿ is a nuclear receptor activated by drugs to treat human disorders of lipid metabolism. Its endogenous ligand is unknown. PPAR¿-dependent gene expression is impaired in mice with tissue-specific inactivation of fatty acid synthase (FAS, which synthesizes palmitate, 16:0), suggesting that FAS is involved in generation of the PPAR¿ cellular ligand. Here we demonstrate the FAS-dependent presence of a specific phospholipid bound to wild type PPAR¿ isolated from the nuclear fraction of mouse liver. FAS-dependent binding of the same Molecular species was also demonstrated for DNA binding-defective (DBD) PPAR¿. Phospholipid binding to wild type as well as DBD PPAR¿ was increased under conditions that induce FAS activity and displaced within minutes by systemic injection of a PPAR¿ agonist.

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。 过氧化物酶体增殖物激活受体是一种核受体，可被药物激活以治疗人类脂质紊乱 新陈代谢.其内源性配体未知。PPAR依赖性基因表达受损 在具有脂肪酸合成酶（FAS，其合成 palmitate，16：0），表明FAS参与了PPAR？细胞配体的产生。 在这里，我们证明了FAS依赖的存在下，一个特定的磷脂结合野生型 从小鼠肝脏的核部分中分离的过氧化物酶体增殖物激活受体。其FAS依赖性结合 分子物种也被证明为DNA结合缺陷（DBD）的PPAR？。在诱导FAS活性的条件下，与野生型以及DBD PPAR <$的磷脂结合增加，并在全身注射PPAR <$激动剂后数分钟内被取代。