在Xenopus laevis中肝增殖器激活受体 (PPAR) 表达的发育模式和转化高潮期间对药物激活剂的反应
Anna Bushong1,2,3, Tyler D Hoskins3, Meredith Scherer3
1Odum School of Ecology, University of Georgia, Athens, Georgia, USA.
概括
非洲爪 (Xenopus laevis) 幼虫在变形过程中表现出动态的过氧体增殖器激活受体 (PPAR). 药物PPAR激活剂没有改变基因表达,这表明X. laevis可能对外来PPAR干扰不敏感.
科学领域:
- 内分泌学
- 发育生物学
- 毒理学
背景情况:
- 过氧体增殖器激活受体 (PPAR) 对脊椎动物的新陈代谢平衡至关重要.
- 两动物,如Xenopus laevis,容易受到内分泌干扰化合物 (EDC) 的影响,这些化合物会破坏脂质代谢.
- 在Xenopus laevis幼虫发育和变形过程中,PPAR表达模式基本上没有特征.
研究的目的:
- 在晚期Xenopus laevis转化过程中描述xPPARα,xPPARβ和xPPARγ亚型的表达.
- 研究药物PPAR激动剂对Xenopus laevis的xPPAR基因表达和顶端终点的影响.
- 评估Xenopus laevis的敏感性,作为研究异生菌的PPAR介导作用的模型.
主要方法:
- 在不同发育阶段对xPPARα/β/γ基因表达的定量分析 (NF 51-66).
- 对 Xenopus laevis 幼虫暴露在 PPAR 激动剂 (皮里尼克酸,贝扎菲布拉特,西普罗菲布拉特) 中.
- 测量顶端终点,包括体重,量化质量指数 (SMI) 和相对肝脏质量.
主要成果:
- 在晚期转化过程中,xPPARα和xPPARγ呈现出动态肝表达,但有显著的例外.
- 只有在转变性高潮结束时,xPPARβ表达得到了上调 (NF 66).
- PPAR激动剂没有改变基因表达;皮里尼克酸降低了女性的身体状况.
结论:
- 在Xenopus laevis转化过程中,xPPAR亚型的动态肝表达表明它们在协调能量流中的作用.
- 缺乏对高剂量的PPAR激活剂的反应表明,Xenopus laevis作为一种敏感模型对异生PPAR干扰研究的潜在局限性.
- 需要进一步的研究,以充分了解环境污染物暴露的两动物的PPAR介导作用.
相关概念视频
Drug Metabolism: Phase I Reactions
3.6K
A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...
3.6K
Cell Specific Gene Expression
13.9K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.9K
Transducer Mechanism: Nuclear Receptors
1.6K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.6K


