TY - JOUR AB - 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. AD - 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 AU - Ma,Baitao AU - Wang,Xuebin AU - Zhang,Rui AU - Niu,Shuai AU - Rong,Zhihua  AU - Ni,Leng AU - Di,Xiao AU - Han,Qin AU - Liu,Changwei DA - 2021/05/01 DO - 10.3892/mmr.2021.11970 IS - 5 JO - Mol Med Rep KW - cigarette smoke extract reactive oxygen species NF‑κB proprotein convertase subtilisin/kexin type 9 low‑density lipoprotein receptor atherosclerosis PY - 2021 SN - 1791-2997 1791-3004 SP - 331 ST - Cigarette smoke extract stimulates PCSK9 production in HepG2 cells via ROS/NF‑κB signaling T2 - Molecular Medicine Reports TI - Cigarette smoke extract stimulates PCSK9 production in HepG2 cells via ROS/NF‑κB signaling UR - https://doi.org/10.3892/mmr.2021.11970 VL - 23 ER -