埃托里可西布增强了阿里尔碳化合物受体活性
Hsiao-Ho Fang1, Jiun Hsu2, Jyan-Gwo Joseph Su1
1Department of Biochemical Science and Technology, National Chiayi University, Chiayi 60004, Taiwan, ROC.
作为一种COX-2抑制剂的 etoricoxib 激活了酸受体 (AhR) 并诱导人体细胞中CYP1A1的表达. 它还与ITE协同作用,可能澄清与NSAID相关的心血管风险.
科学领域:
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 埃托里科西布是一种选择性循环氧基因酶-2 抑制剂,具有已知的心血管问题的NSAID.
- 基碳化合物受体 (AhR) 调节异生菌的新陈代谢和生理功能.
- ITE是一种内源的AhR激活剂,可诱导CYP1A1的表达.
研究的目的:
- 为了研究 etoricoxib 与基碳化合物受体 (AhR) 信号通路的相互作用.
- 为了确定 etoricoxib 是否调节 CYP1A1 的表达.
- 探索 etoricoxib 和 ITE 对 AhR 活动的潜在协同效应.
主要方法:
- 使用小鼠Hepa-1c1c7和人类HepG2细胞进行基于细胞的测定.
- 测量CYP1A1的mRNA和蛋白质表达.
- 通过AHRE记者测定对AhR转录活性进行评估.
- 使用AhR抗剂 (CH-223191) 的抑制研究.
主要成果:
- 埃托里可西布以剂量依赖的方式诱导CYP1A1mRNA和蛋白质表达和AhR转录活性.
- 这些效应依赖于AhR信号,并被CH-223191.1抑制.
- 埃托里可西布促进了AhR从细胞质到细胞核的转移.
- 埃托里可西布与ITE对人体细胞中CYP1A1表达具有协同作用,特别是在过度表达AhR的细胞中.
结论:
- 在老鼠和人体细胞中,埃托里可西布作为AhR激动剂起作用.
- 埃托里可西布增强ITE诱导的CYP1A1表达,这表明AhR通路内的复杂相互作用.
- 对埃托利克西布对内皮细胞和心肌细胞的影响进行进一步的研究是必要的,以阐明与COX-2抑制剂相关的心血管风险.
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