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类药物激活AMP激活的蛋白激酶在体外和体内
Wei Sun1, Tzong-Shyuan Lee, Minjia Zhu
1Division of Biomedical Sciences, University of California, Riverside, Riverside, CA 92521-0121, USA.
Circulation
|November 23, 2006
概括
斯坦丁激活AMP激活蛋白激酶 (AMPK),增强内皮氧化合成酶 (eNOS) 的活性. 这种AMPK激活解释了通过促进氧化生产和血管生成来促进他的心血管益处.
科学领域:
- 心血管药理学心血管药理学
- 分子生物学分子生物学
- 细胞的新陈代谢
背景情况:
- 类药物对心血管有好处,部分原因是增加了氧化 (NO) 的生物可用性.
- AMP激活蛋白激酶 (AMPK) 对于细胞能量和新陈代谢至关重要.
- 需要阐明他类药物,AMPK激活和通过内皮NO合成酶 (eNOS) 生产NO之间的关系.
研究的目的:
- 调查他类药物是否激活AMPK.
- 要确定激活的AMPK是否通过eNOS调节NO的产生和血管生成.
- 探索他类药物的心血管性作用背后的机制.
主要方法:
- 人的静脉内皮细胞用阿托瓦斯塔丁治疗.
- 西部涂抹和SAMS测定评估了AMPK及其目标酸化.
- 抑制研究使用主导负AMPK (Ad-AMPK-DN) 和化合物C.
- 在体内研究中,小鼠接受了阿托瓦斯塔丁.
主要成果:
- 阿托瓦斯塔丁以剂量和时间依赖的方式增加了内皮细胞中的AMPK酸化和活性.
- AMPK的激活导致了乙-CoA碳酸酶和eNOS的酸化.
- 抑制AMPK阻断了阿托瓦斯塔丁诱导的NO产生,cGMP积累和血管生成.
- 在体内,阿托瓦斯塔丁在小鼠大动脉和心肌中增加了AMPK,ACC和eNOS酸化.
结论:
- 类他类药物通过Thr-172酸化快速激活AMPK,在体外和体内.
- 这种激活刺激了eNOS,导致NO的产量增加.
- 通过他类药物的AMPK激活为其心血管保护作用提供了一种新的机制.
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