Lee Gi Ho, Lee Seung Yeon, Zheng Chuanfeng, Pham Hoa Thi, Kim Chae Yeon, Kim Mi Yeon, Han Eun Hee, Hwang Yong Pil, Jeong Hye Gwang
College of Pharmacy, Chungnam National University, Daejeon, 305-764 Republic of Korea.
Drug & Disease Target Research Team, Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI), Cheongju, 28119 Republic of Korea.
Toxicol Res. 2022 Feb 5;38(3):355-364. doi: 10.1007/s43188-022-00121-9. eCollection 2022 Jul.
3-Caffeoyl-4-dicaffeoylquinic acid (CDCQ) is a natural chlorogenic acid isolated from that protects against oxidative stress, inflammation, and cancer. Nitric oxide (NO) plays a physiologically beneficial role in the cardiovascular system, including vasodilation, protection of endothelial cell function, and anti-inflammation. However, the effect of CDCQ on NO production and eNOS phosphorylation in endothelial cells is unclear. We investigated the effect of CDCQ on eNOS phosphorylation and NO production in human endothelial cells, and the underlying signaling pathway. CDCQ significantly increased NO production and the phosphorylation of eNOS at Ser1177. Additionally, CDCQ induced phosphorylation of PKA, CaMKII, CaMKKβ, and AMPK. Interestingly, CDCQ increased the intracellular Ca level, and L-type Ca channel (LTCC) blockade significantly attenuated CDCQ-induced eNOS activity and NO production by inhibiting PKA, CaMKII, CaMKKβ, and AMPK phosphorylation. These results suggest that CDCQ increased eNOS phosphorylation and NO production by Ca-dependent phosphorylation of PKA, CaMKII, CaMKKβ, and AMPK. Our findings provide evidence that CDCQ plays a pivotal role in the activity of eNOS and NO production, which is involved in the protection of endothelial dysfunction.
3-咖啡酰-4-二咖啡酰奎宁酸（CDCQ）是一种从[具体来源未给出]中分离出的天然绿原酸，具有抗氧化应激、抗炎和抗癌作用。一氧化氮（NO）在心血管系统中发挥着生理有益作用，包括血管舒张、保护内皮细胞功能和抗炎。然而，CDCQ对内皮细胞中NO生成和eNOS磷酸化的影响尚不清楚。我们研究了CDCQ对人内皮细胞中eNOS磷酸化和NO生成的影响及其潜在信号通路。CDCQ显著增加了NO生成以及eNOS在Ser1177位点的磷酸化。此外，CDCQ诱导了PKA、CaMKII、CaMKKβ和AMPK的磷酸化。有趣的是，CDCQ增加了细胞内钙离子水平，而L型钙通道（LTCC）阻滞剂通过抑制PKA、CaMKII、CaMKKβ和AMPK磷酸化，显著减弱了CDCQ诱导的eNOS活性和NO生成。这些结果表明，CDCQ通过PKA、CaMKII、CaMKKβ和AMPK的钙依赖性磷酸化增加了eNOS磷酸化和NO生成。我们的研究结果提供了证据，表明CDCQ在eNOS活性和NO生成中起关键作用，这与保护内皮功能障碍有关。
