Wogonin ameliorates lipotoxicity-induced apoptosis of cultured vascular smooth muscle cells via interfering with DAG-PKC pathway
Wogonin ameliorates lipotoxicity-induced apoptosis of cultured vascular smooth muscle cells via interfering with DAG-PKC pathway
复制标题
汉黄芩素通过干扰 DAG-PKC 通路改善脂毒性诱导的培养血管平滑肌细胞凋亡
DOI：
10.1038/aps.2011.120
复制
发表时间：
2011-12-01
影响因子：
8.2
通讯作者：
Zhang, Jun-jian
中科院分区：
文献类型：
--
作者：
Liu, Yu-min;Wang, Xiong;Zhang, Jun-jian
目的：探讨黄芩苷（5,7 -二羟基-8-甲氧基黄酮）对脂肪中毒诱导的血管平滑肌细胞（VSMCs）凋亡的影响及其机制。方法：采用体外培养的VSMCs。棕榈酸酯（0.75 mmol/L）诱导VSMCs凋亡，TUNEL法检测。Western blot检测蛋白和磷酸化蛋白的表达水平。结果：10、25和50 μmol/L枸杞子素对棕榈酸盐诱导的VSMCs细胞凋亡和内质网应激均有浓度依赖性和时间依赖性。Wogonin （50 μmol/L）可减少棕榈酸盐诱导的活性氧（ROS）生成。内质网络应激抑制剂4-苯基丁酸（5 mmol/L）可显著降低棕榈酸诱导的凋亡细胞，并阻断乌根素（25 μmol/L）的抗凋亡作用。Wogonin（10、25和50 μmol/L）显著降低棕榈酸处理的vsmc细胞内二酰基甘油（DAG）的积累和磷酸化PKCs的表达水平。结论：我们的研究结果表明，沃草精素通过抑制细胞内DAG积累和随后抑制PKC磷酸化来抑制脂肪毒性诱导的VSMCs凋亡。枸杞素具有预防和治疗动脉粥样硬化的治疗潜力。
Aim:To investigate the effects of wogonin (5, 7-dihydroxy-8-methoxyflavone) extracted from Scutellaria baicalensis Georgi (S baicalensis) on lipotoxicity-induced apoptosis of vascular smooth muscle cells (VSMCs) and the underlying mechanisms.Methods:Cultured VSMCs were used. Apoptosis of VSMCs was induced by palmitate (0.75 mmol/L), and detected using TUNEL assay. The expression levels of protein and phosphorylated protein were measured using Western blot analysis.Results:Treatment of VSMCs with wogonin (10, 25 and 50 μmol/L) significantly attenuated the apoptosis and endoplasmic reticulum (ER) stress induced by palmitate in concentration-and time-dependent manners. Wogonin (50 μmol/L) decreased palmitate-induced reactive oxygen species (ROS) generation. The ER stress inhibitor 4-phenyl butyric acid (5 mmol/L) significantly decreased palmitate-induced apoptotic cells, and occluded the anti-apoptotic effect of wogonin (25 μmol/L). Wogonin (10, 25 and 50 μmol/L) significantly reduced the intracellular diacylglycerol (DAG) accumulation and expression levels of phosphorylated PKCs in palmitate-treated VSMCs.Conclusion:Our results suggest that wogonin inhibits lipotoxicity-induced apoptosis of VSMCs via suppressing the intracellular DAG accumulation and subsequent inhibition of PKC phosphorylation. Wogonin has therapeutic potential for the prevention and treatment of atherosclerosis.