希斯胺在人类血管内皮细胞中上调了内皮氧化合成酶的基因表达
Huige Li1, Christian Burkhardt, Ulf-Rüdiger Heinrich
1Department of Pharmacology, Johannes Gutenberg University, Obere Zahlbacher Strasse 67, D-55131 Mainz, Germany.
Circulation
|April 23, 2003
概括
组胺,通过H1受体,通过CaMK II信号增加内皮氧化合成酶 (eNOS) 表达. 这种eNOS上调有利于正常条件,但在氧化应激期间可能有害.
科学领域:
- 内皮细胞生物学 内皮细胞生物学
- 分子信号传递是分子信号传递.
- 血管药理学 血管药理学
背景情况:
- 已知胺对内皮氧化合成酶 (eNOS) 活动的短期影响,但长期影响尚不清楚.
- 血管对组胺的反应严重依赖eNOS功能.
研究的目的:
- 研究组胺在内皮细胞中对eNOS基因表达和功能的长期影响.
主要方法:
- 使用了人类静脉内皮细胞 (HUVEC) 和EA.hy 926细胞.
- 使用RNase保护试验和电子显微镜免疫细胞化学评估了eNOS mRNA和蛋白质表达.
- 研究的信号通路涉及H1受体对抗性 (美皮拉胺),CaMK II (KN-93抑制剂) 和eNOS促进体活性 (露西法酶记者测定).
- 在正常和氧化应激条件下测量了氧化生产和反应性氧物种的产生.
主要成果:
- 基因组胺上调了eNOS mRNA和蛋白质表达,由H1受体和CaMK II信号传导介导.
- 海斯胺增加了eNOS促进剂活性.
- 在正常情况下,由组胺诱导的eNOS上调会增强氧化的产生.
- 在氧化应激下,由组胺诱导的eNOS产生了反应性氧物种,而不是氧化.
结论:
- H1受体刺激通过一种依赖于CaMK II的途径增加内皮细胞中的eNOS转录.
- 在正常生理条件下,因斯坦胺对eNOS的上调调节可能具有保护作用.
- 这种上调在氧化应激下可能是有害的,导致eNOS产生活性氧物种.
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