芹菜素诱导的 HIF-1α 抑制作用改善了 AngⅡ/缺氧刺激或 HIF-1α 过表达 H9c2 细胞中的异常糖脂代谢。
Apigenin-induced HIF-1α inhibitory effect improves abnormal glucolipid metabolism in AngⅡ/hypoxia-stimulated or HIF-1α-overexpressed H9c2 cells.
机构信息
Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China; Department of Pharmacy, The Affiliated Children's Hospital of Soochow University, Suzhou 215003, Jiangsu Province, China.
Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China.
出版信息
Phytomedicine. 2019 Sep;62:152713. doi: 10.1016/j.phymed.2018.10.010. Epub 2018 Oct 10.
BACKGROUND
Apigenin, a natural flavonoid compound, can improve the myocardial abnormal glucolipid metabolism and down-regulate the myocardial hypoxia inducible factor-1α (HIF-1α) in hypertensive cardiac hypertrophic rats. However, whether or not the ameliorative effect of glucolipid metabolism is from the reduction of HIF-1α expression remains uncertain.
PURPOSE
This study aimed to investigate the exact relationship between them in angiotensin Ⅱ (Ang Ⅱ)/hypoxia-stimulated or HIF-1α overexpressed H9c2 cells.
METHODS
Two cell models with Ang Ⅱ/hypoxia-induced hypertrophy and HIF-1α overexpression were established. After treatment of the cells with different concentrations of apigenin, the levels of total protein, free fatty acids (FFA), and glucose were detected by the colorimetric method, the level of atrial natriuretic peptide (ANP) was detected by the ELISA method, and the expressions of HIF-1α, peroxisome proliferator-activated receptor α/γ (PPARα/γ), carnitine palmitoyltmnsferase-1 (CPT-1), pyruvate dehydrogenase kinase-4 (PDK-4), glycerol-3-phosphate acyltransferase genes (GPAT), and glucose transporter-4 (GLUT-4) proteins were detected by the Western blot assay.
RESULTS
Following treatment of the both model cells with apigenin 1-10 μM for 24 h, the levels of intracellular total protein, ANP, and FFA were decreased, while the level of cultured supernatant glucose was increased. Importantly, apigenin treatment could inhibit the expressions of HIF-1α, PPARγ, GPAT, and GLUT-4 proteins, and increase the expressions of PPARα, CPT-1, and PDK-4 proteins.
CONCLUSION
Apigenin could exert an ameliorative effect on abnormal glucolipid metabolism in AngⅡ/hypoxia-stimulated or HIF-1α-overexpressed H9c2 cells, and its mechanisms were associated with the inhibition of HIF-1α expression and subsequent upregulation of PPARα-mediated CPT-1 and PDK-4 expressions and downregulation of PPARγ-mediated GPAT and GLUT-4 expressions.
背景
芹菜素是一种天然黄酮类化合物，可改善高血压性心肌肥厚大鼠心肌异常糖脂代谢，并下调心肌低氧诱导因子-1α（HIF-1α）。然而，糖脂代谢的改善作用是否来自于 HIF-1α 表达的减少尚不确定。
目的
本研究旨在探讨芹菜素在血管紧张素Ⅱ（Ang Ⅱ）/缺氧刺激或 HIF-1α 过表达的 H9c2 细胞中，两者之间的确切关系。
方法
建立 Ang Ⅱ/缺氧诱导的肥大和 HIF-1α 过表达的两种细胞模型。用不同浓度的芹菜素处理细胞后，用比色法检测总蛋白、游离脂肪酸（FFA）和葡萄糖水平，用 ELISA 法检测心钠肽（ANP）水平，用 Western blot 法检测 HIF-1α、过氧化物酶体增殖物激活受体α/γ（PPARα/γ）、肉碱棕榈酰转移酶-1（CPT-1）、丙酮酸脱氢酶激酶-4（PDK-4）、甘油-3-磷酸酰基转移酶基因（GPAT）和葡萄糖转运蛋白-4（GLUT-4）蛋白的表达。
结果
用 1-10μM 芹菜素处理两种模型细胞 24 小时后，细胞内总蛋白、ANP 和 FFA 水平降低，培养上清液中葡萄糖水平升高。重要的是，芹菜素处理可抑制 HIF-1α、PPARγ、GPAT 和 GLUT-4 蛋白的表达，增加 PPARα、CPT-1 和 PDK-4 蛋白的表达。
结论
芹菜素可改善 Ang Ⅱ/缺氧刺激或 HIF-1α 过表达的 H9c2 细胞异常糖脂代谢，其机制与抑制 HIF-1α 表达，随后上调 PPARα 介导的 CPT-1 和 PDK-4 表达，下调 PPARγ 介导的 GPAT 和 GLUT-4 表达有关。
Zotero 插件