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首页> 外文学位 >Modulation of peroxisome proliferator-activated receptor alpha-mediated gene transcription of rat peroxisomal acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase by members of the nuclear hormone receptor superfamily.
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Modulation of peroxisome proliferator-activated receptor alpha-mediated gene transcription of rat peroxisomal acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase by members of the nuclear hormone receptor superfamily.

机译：核激素受体超家族成员对过氧化物酶体增殖物激活的受体α介导的大鼠过氧化物酶体酰基辅酶A氧化酶和烯酰辅酶A水合酶/ 3-羟酰基辅酶A脱氢酶的基因转录的调节。

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摘要

Peroxisome proliferator-activated receptors (PPAR) are members of the nuclear hormone receptor superfamily that serve as ligand-activated transcription factors regulating the expression of genes involved in lipid metabolism (peroxisomal β-oxidation), adipogenesis, inflammation, and glucose metabolism. PPARs are activated by a diverse group of compounds termed peroxisome proliferators, which include the fibrate family of hypolipidemic drugs, eicosanoids, antidiabetic thiazolidinediones, as well as naturally occurring and synthetic mono- and polyunsaturated fatty acids. Upon binding of ligand, PPARs heterodimerize with the 9-cis -retinoic acid receptor (RXRα) and bind to cognate binding sequences termed peroxisome proliferator-response elements (PPRE) found in the promoter regions of target genes. PPAR-mediated gene transcription is a complex and dynamic event involving a myriad of cellular factors. This thesis examines the role of various members of the nuclear hormone receptor superfamily in modulating gene transcription by PPARs. In particular, this thesis focuses on the genes encoding the first two enzymes of the peroxisomal β-oxidation pathway, acyl-CoA oxidase (AOx) and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (HD).; The results presented illustrate the involvement of thyroid hormone receptor α, RevErb α, constitutive androstane receptor β (CARβ), and the short heterodimer partner (SBP) in differentially modulating PPARα-mediated gene transcription from both the AOx- and HD-PPREs. Furthermore, subtype- and response element-dependent differences in gene transcription between two PPAR subtypes, α and γ, are also demonstrated. The conclusions drawn from this research further support the hypothesis that PPAR-mediated gene transcription from PPREs is integrated with the transcriptional activities of various members of the nuclear hormone receptor superfamily, as well as with a variety of cellular coactivators and corepressors, and can be influenced by the availability of ligand so as to ensure a correct transcriptional response to extra- and intracellular stimuli from appropriate target genes. The research contained herein establishes a framework for understanding normal and dysfunctional lipid metabolism and provides an impetus for further exploration of the molecular mechanisms of PPAR-mediated gene transcription.
机译：过氧化物酶体增殖物激活受体（PPAR）是核激素受体超家族的成员，它们充当配体激活的转录因子，调节参与脂质代谢（过氧化物酶体β-氧化），脂肪形成，炎症和葡萄糖代谢的基因的表达。 PPAR被称为过氧化物酶体增生剂的各种化合物激活，这些化合物包括降血脂药的纤维状家族，类花生酸，抗糖尿病的噻唑烷二酮，以及天然存在的和合成的单和多不饱和脂肪酸。结合配体后，PPAR与9- 顺式-视黄酸受体（RXRα）异源二聚体，并与在目标基因启动子区域中发现的过氧化物酶体增殖物反应元件（PPRE）的同源结合序列结合。 PPAR介导的基因转录是一个复杂而动态的事件，涉及多种细胞因子。本文探讨了核激素受体超家族的各个成员在调节PPARs基因转录中的作用。特别是，本论文着眼于编码过氧化物酶体β-氧化途径的前两种酶的基因，即酰基辅酶A氧化酶（AOx）和烯酰基辅酶A水合酶/ 3-羟酰基辅酶A脱氢酶（HD）。呈现的结果说明了甲状腺激素受体α，RevErbα，组成型雄甾烷受体β（CARβ）和短异二聚体伴侣（SBP）参与了AOx和HD-PPREs的PPARα介导基因转录的差异调控。此外，还证明了两种PPAR亚型α和γ之间基因转录的亚型和响应元件依赖性。这项研究得出的结论进一步支持了以下假设：PPRE介导的PPAR介导的PPRE基因转录与核激素受体超家族的各个成员的转录活性以及多种细胞共激活因子和共加压因子整合在一起，并且可能受到影响通过配体的可用性来确保对来自适当靶基因的细胞外和细胞内刺激的正确转录反应。本文包含的研究为理解正常和功能异常的脂质代谢建立了框架，并为进一步探索PPAR介导的基因转录的分子机制提供了动力。

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  • 作者

    Kassam, Altaf.;

  • 作者单位

    University of Alberta (Canada).;

  • 授予单位 University of Alberta (Canada).;
  • 学科 Biology Cell.; Biology Molecular.
  • 学位 Ph.D.
  • 年度 2001
  • 页码 239 p.
  • 总页数 239
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;分子遗传学;
  • 关键词

  • 入库时间 2022-08-17 11:46:53

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