氧化酸胆激活NOX1介导的氧化应激反应并改变心脏细胞中的葡萄糖代谢
Anna A Licznerska1,2, Caitlin M Pavelec1,3, Priyanka Rawat1
1Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, United States.
American journal of physiology. Cell physiology
|August 25, 2025
概括
氧化酸胆 (OxPCs) 有助于心血管疾病. 在改变心脏基因表达的小鼠中减少OxPCs. 在心脏细胞中,OxPCs改变新陈代谢和能量生产,NOX1调解氧化还原应激.
科学领域:
- 心血管生物学
- 氧化应激研究
- 细胞代谢
背景情况:
- 心脏代谢综合征涉及增加的全身氧化应激和心血管疾病.
- 氧化酸胆 (OxPCs) 与心血管疾病的进展有关.
- 减少OxPCs对小鼠的影响心脏基因表达.
研究的目的:
- 在体外研究心肌细胞对OxPCs的反应.
- 确定OxPC诱导的细胞变化的分子机制.
- 探索NOX1在OxPC中介的氧化还原应激中的作用.
主要方法:
- 暴露H9c2心肌细胞氧化酸胆混合物 (OxPAPC).
- 转录分析以确定受影响的通路 (例如Nrf2通路).
- 测量反应性氧物种 (ROS) 生产和代谢转移 (例如,酸盐路径,糖解,ATP 生产).
- 研究MEK-ERK MAPK路径的参与.
主要成果:
- 氧PAPC治疗通过Nrf2上调了氧化还原调节基因 (例如Hmox1).
- OxPAPC通过NADPH氧化酶1 (Nox1) 诱导ROS的产生,增加氧化谷.
- 代谢转变包括酸路径激活,糖解抑制和ATP产生减少.
- 通过MEK- ERK MAPK通路的激活,OxPAPC降低了氧化酸化.
结论:
- 心脏肌细胞通过上调氧化还原通路和改变能量代谢来响应oxPCs.
- NOX1被确定为心脏细胞中OxPC诱导的氧化还原应激的新型媒介.
- 这些发现表明由NOX1介导的OxPC诱导的氧化还原应激可能导致心脏代谢综合征的心脏细胞损伤.
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