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白杨素通过干扰 DAG-PKC 通路改善脂毒性诱导的血管平滑肌细胞凋亡。

Wogonin ameliorates lipotoxicity-induced apoptosis of cultured vascular smooth muscle cells via interfering with DAG-PKC pathway.

机构信息

Department of Neurology, Zhongnan Hospital of Wuhan University, China.

出版信息

Acta Pharmacol Sin. 2011 Dec;32(12):1475-82. doi: 10.1038/aps.2011.120. Epub 2011 Oct 10.

Abstract

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.

摘要

目的

研究黄芩素(5,7-二羟基-8-甲氧基黄酮)对脂毒性诱导的血管平滑肌细胞(VSMCs)凋亡的影响及其作用机制。

方法

培养 VSMCs,用软脂酸(0.75mmol/L)诱导 VSMCs 凋亡,采用 TUNEL 法检测。用 Western blot 分析检测蛋白和磷酸化蛋白的表达水平。

结果

黄芩素(10、25 和 50μmol/L)处理 VSMCs 可呈浓度和时间依赖性地显著减轻软脂酸诱导的细胞凋亡和内质网(ER)应激。黄芩素(50μmol/L)可减少软脂酸诱导的活性氧(ROS)生成。ER 应激抑制剂 4-苯丁酸(5mmol/L)可显著减少软脂酸诱导的凋亡细胞,并阻断黄芩素(25μmol/L)的抗凋亡作用。黄芩素(10、25 和 50μmol/L)可显著降低软脂酸处理的 VSMCs 中细胞内二酰基甘油(DAG)的积累和磷酸化蛋白激酶 C(PKC)的表达水平。

结论

我们的结果表明,黄芩素通过抑制细胞内 DAG 积累和随后抑制 PKC 磷酸化来抑制脂毒性诱导的 VSMCs 凋亡。黄芩素具有预防和治疗动脉粥样硬化的治疗潜力。

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