Antagonist of Prostaglandin E-2 Receptor 4 Induces Metabolic Alterations in Liver of Mice
Antagonist of Prostaglandin E-2 Receptor 4 Induces Metabolic Alterations in Liver of Mice
复制标题
前列腺素 E-2 受体 4 拮抗剂诱导小鼠肝脏代谢改变
DOI：
10.1021/pr501236y
复制
发表时间：
2015
影响因子：
4.4
通讯作者：
Tang Huiru
中科院分区：
文献类型：
--
作者：
Li Ning;Zhang Limin;An Yanpeng;Zhang Lulu;Song Yipeng;Wang Yulan;Tang Huiru
前列腺素E2受体4(EP4)是前列腺素E2的受体之一，在多种生物学功能中发挥重要作用。EP4拮抗剂已被用作抗炎药物。为了从整体上研究EP4拮抗剂L-161982对内源性代谢的影响，我们采用小鼠模型，获得了暴露于EP4拮抗剂L-161982的小鼠的血清、肝脏和尿液等多种生物基质的代谢和转录图谱。我们发现，这种EP4拮抗剂引起了脂肪酸代谢、胆碱代谢和核苷酸代谢的显著变化。EP4拮抗剂暴露也可引起小鼠氧化应激。我们的研究是第一次报道与EP4拮抗剂相关的代谢改变的信息。这些信息有助于我们进一步了解EP4的现有和新的生物学功能。
Prostaglandin E2receptor 4 (EP4) is one of the receptors for prostaglandin E2and plays important roles in various biological functions. EP4 antagonists have been used as anti-inflammatory drugs. To investigate the effects of an EP4 antagonist (L-161982) on the endogenous metabolism in a holistic manner, we employed a mouse model, and obtained metabolic and transcriptomic profiles of multiple biological matrixes, including serum, liver, and urine of mice with and without EP4 antagonist (L-161982) exposure. We found that this EP4 antagonist caused significant changes in fatty acid metabolism, choline metabolism, and nucleotide metabolism. EP4 antagonist exposure also induced oxidative stress to mice. Our research is the first of its kind to report information on the alteration of metabolism associated with an EP4 antagonist. This information could further our understanding of current and new biological functions of EP4.