P300/CBP通过间歇性缺氧来调节HIF-1-依赖的交感激活和高血压
Ning Wang1, Xiaoyu Su1, David Sams1
1Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, The University of Chicago, Chicago, Illinois.
American journal of respiratory cell and molecular biology
|October 24, 2023
概括
阻塞性睡眠呼吸暂停会导致间歇性缺氧,增加交感神经活动和高血压. 这项研究表明,p300/CBP的HIF-1α乙化激活了Nox转录,导致高血压.
科学领域:
- 身体生理学 身体生理学
- 分子生物学分子生物学
- 心血管研究研究心血管研究
背景情况:
- 阻塞性睡眠呼吸暂停 (OSA) 与间歇性缺氧 (IH) 有关,导致交感性过度活动和高血压.
- 缺氧诱导因子-1 (HIF-1) 激活NADPH氧化酶 (Nox) 有助于IH的自主功能障碍.
- 氨酸乙化调节基因转录,并与生理和病理过程有关.
研究的目的:
- 调查p300/CBP的HIF-1α乙化是否激活了Nox转录,导致IH中的交感激活和高血压.
主要方法:
- 实验中使用了染细胞12细胞和暴露于IH的老鼠.
- 使用选择性抑制剂CTK7A.实现了p300/CBP活性的抑制.
- 测量包括基因转录,蛋白质水平,活性氧物种和血压.
主要成果:
- IH增加了p300/CBP活性,HIF-1α乙化和细胞中的Nox转录,CTK7A阻断了这些效应.
- 接受IH治疗的老鼠表现出高上腺素,血压,p300/CBP,HIF-1α,Nox基因表达和活性氧物种.
- 在老鼠中,CTK7A治疗阻止了这些IH诱导的反应.
结论:
- 通过p300/CBP对HIF-1α的氨酸乙化是驱动IH中的交感激活和高血压的关键机制.
- 针对p300/CBP介导的乙化可能为OSA相关并发症提供治疗策略.
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