Cigarette smoke extract stimulates PCSK9 production in HepG2 cells via ROS/NF‑κB signaling

Ma,Baitao; Wang,Xuebin; Zhang,Rui; Niu,Shuai; Rong,Zhihua; Ni,Leng; Di,Xiao; Han,Qin; Liu,Changwei

doi:10.3892/mmr.2021.11970

Cigarette smoke extract stimulates PCSK9 production in HepG2 cells via ROS/NF‑κB signaling

Authors:
- Baitao Ma
- Xuebin Wang
- Rui Zhang
- Shuai Niu
- Zhihua Rong
- Leng Ni
- Xiao Di
- Qin Han
- Changwei Liu
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Affiliations: Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China, Department of Vascular Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China, Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy, Beijing 100005, P.R. China
Published online on: March 8, 2021 https://doi.org/10.3892/mmr.2021.11970
Article Number: 331
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cigarette smoke (CS) exposure is a risk factor for dyslipidemia and atherosclerosis. Reduced expression of low‑density lipoprotein receptor (LDLR) in hepatocytes may be one of the underlying mechanisms for these disorders. The aim of the present study was to investigate the molecular mechanism underlying the regulatory effect of CS extract (CSE) on proprotein convertase subtilisin/kexin type 9 (PCSK9) and low LDLR expression in HepG2 cells. PCSK9 and LDLR mRNA and protein expression levels in HepG2 cells were evaluated after CSE treatment via reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. In addition, total intracellular reactive oxygen species (ROS) production was determined via 2,7‑dichlorofluorescein diacetate fluorescence. CSE significantly increased PCSK9 expression and inhibited LDLR expression in a time‑ and concentration‑dependent manner. Furthermore, CSE significantly induced ROS production and nuclear factor κB (NF‑κB) activation. However, pretreatment with a ROS scavenger or an NF‑κB inhibitor significantly attenuated the CSE‑induced changes in PCSK9 and LDLR expression. In addition, pretreatment with melatonin markedly reduced ROS production, NF‑κB activation and PCSK9 expression, and increased LDLR expression in the CSE‑treated cells. These data suggest that melatonin inhibits CSE‑regulated PCSK9 and LDLR production in HepG2 cells via ROS/NF‑κB signaling.

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