蛋白酸酶4通过降低HUVECs中的NNOS酸化在血清633的水平来调解棕酸诱导的内皮功能障碍
Zhengwei Liang1, Gang Sun1, Junshi Zhang1
1Department of Pathophysiology, Guizhou Medical University, Guiyang, China; Guizhou Provincial Key Laboratory of Pathogenesis & Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, China.
Experimental cell research
|March 21, 2024
概括
棕酸通过激活NADPH氧化酶/ROS引起内皮功能障碍,从而通过蛋白质酸酶4 (PP4) 减少ENOS酸化. 向PP4可以治疗内皮功能障碍和血管疾病.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 细胞信号传输 细胞信号传输
背景情况:
- 由于和自由脂肪酸 (FFAs) 的内皮功能障碍 (ED) 导致动脉样硬化.
- 由于FFA引起的ED的确切机制尚未完全理解.
研究的目的:
- 阐明棕酸 (PA) 诱导ED的分子机制.
- 为了确定ED的潜在治疗点.
主要方法:
- 研究了NADPH氧化酶 (NOX) /ROS信号通路在PA诱导的ED中的作用.
- 使用蛋白质酸酶抑制剂 (Okadaic酸,Fostriecin) 和抗氧化剂 (N-乙半氨酸,Apocynin).
- 采用基因沉默技术 (siRNA) 对NOX子单元,PP4和PP2A催化子单元,并进行共免疫沉测试.
主要成果:
- PA激活了NOX/ROS,导致PP4和PP2A的激活,降低了Ser633和Ser1177.7.的eNOS酸化.
- 通过PA降低PP4R2的调节对于减少eNOS Ser633酸化和ED至关重要.
- PP4R2过度表达挽救了eNOS酸化,氧化生产和内皮细胞功能.
- 发现PP4R2和PP4c与eNOS相互作用.
结论:
- 通过NOX/ROS途径降低PP4R2表达,激活PP4,并随后在Ser633.3处去酸化eNOS,PA诱导ED.
- 蛋白酸酶4 (PP4) 是一种新的治疗点,用于内皮功能障碍和相关的血管疾病.
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