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KMID : 1134820200490090919
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Journal of the Korean Society of Food Science and Nutrition
2020 Volume.49 No. 9 p.919 ~ p.924
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Isoeugenol Inhibits PCSK9 in HepG2 Cells
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Choi Hyo-Kyoung
Chung Min-Yu
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Abstract
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Hypercholesterolemia is a major cause of a number of different chronic diseases, including atherosclerosis. Statins for the treatment of hypercholesterolemia induce transactivation of low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 interferes with LDL cholesterol and its receptor binding, promoting LDLR degradation and thereby increasing circulating LDL cholesterol. In the current study, HepG2 cells were treated with 10% delipidated serum (DLPS) in the presence or absence of isoeugenol. Lipid depletion increased both LDLR and PCSK9 protein expression levels in HepG2 cells, and isoeugenol inhibited PCSK9 in HepG2 cells. The objective of this study was to investigate the mechanism by which isoeugenol inhibits PCSK9 and subsequently increases LDLR protein expression HepG2 cells under lipid depletion conditions. A non-toxic level of isoeugenol reduced PCSK9 protein expression without affecting LDLR protein expression. Lipid depletion enhanced gene expression of LDLR, PCSK9, and their transcription factors SREBP2 and HNF1α in HepG2 cells. Isoeugenol significantly attenuated LDLR, PCSK9, and SREBP2 gene expression (P<0.0001), but not HNF1α. Consistently, isoeugenol also markedly reduced SREBP2 protein expression, but not HNF1α. This suggests that isoeugenol-mediated SREBP2 down- regulation reduced LDLR and PCSK9 gene expression, and attenuated PCSK9 expression contributed to maintenance of LDLR protein expression in HepG2 cells under lipid depletion conditions. In DLPS-treated HepG2 cells, isoeugenol dose-dependently reduced statin-mediated elevation of PCSK9 protein expression. This study suggests isoeugenol as a potential statin co-treatment material and PCSK9 inhibitor.
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KEYWORD
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isoeugenol, PCSK9, LDL receptor, SREBP2, HepG2
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