Apigenin-induced HIF-1α inhibitory effect improves abnormal glucolipid metabolism in AngⅡ/hypoxia-stimulated or HIF-1α-overexpressed H9c2 cells

Abstract

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.

Keywords: Apigenin; HIF-1α; Myocardial cells; Myocardial glucolipid metabolism.