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KMID : 1134820170460111278
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Journal of the Korean Society of Food Science and Nutrition
2017 Volume.46 No. 11 p.1278 ~ p.1285
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Allium tuberosum Reverses PCSK9-Mediated LDLR Degradation by Inhibition of HNF1α
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Choi Hyo-Kyoung
Kim Hyo-Jin
Hwang Jin-Taek
Chung Min-Yu
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Abstract
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Accumulation of excess low density lipoprotein (LDL) cholesterol in the blood can initiate and accelerate atherosclerosis. Statins mediate the transactivation of proprotein convertase subtilisin/kexin type 9 (PCSK9), which in turn limits their cholesterol-lowering effects via LDL receptor (LDLR) degradation. The objective of this study was to investigate whether or not Allium tuberosum (AT) regulates LDLR and PCSK9. Mice were fed a low fat control diet (LD) or Western diet (WD) supplemented with AT (1%, w/w). AT significantly attenuated total and LDL cholesterol levels in mice fed WD (P<0.05). AT also significantly inhibited hepatic PCSK9 gene expression (P<0.05) while AT maintained hepatic LDLR gene expression. To further investigate AT-mediated PCSK9 regulation, HepG2 cells were treated with 10% delipidated serum (DLPS) in the presence or absence of AT. Non-toxic level of AT dose-dependently increased the LDLR protein level, and AT at 400 μg/mL markedly inhibited PCSK9 protein expression. Similarly, AT significantly increased LDLR gene expression, whereas it significantly down-regulated PCSK9 gene expression. AT-mediated reduction of PCSK9 gene expression is likely due to decreased hepatic nuclear factor 1α (HNF1α) expression, but not SREBP2 in HepG2 cells under lipid-depleted conditions. AT-mediated PCSK9 inhibition contributed to LDLR protein stabilization via protection against LDLR lysosomal degradation in HepG2 cells under lipid-depleted conditions. Further investigation is warranted to determine the active components of AT and whether or not these components are effective in reducing hypercholesterolemia.
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KEYWORD
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PCSK9, LDL receptor, HNF1α, HepG2, Western diet
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