title: Cytoprotective Effect of Makgeolli Lees on Paraquat Induced Oxidative Stress in A549 Cells via Activation of NRF2 and Antioxidant Genes.
abstract: Makgeolli lees (ML) has several physiological effects such as antioxidant, antidiabetic, and anticancer properties, but its biological functions have not been determined definitively. Here, we tested whether ML has a cytoprotective effect on paraquat (PQ)-induced oxidative stress in the human lung carcinoma cell line A549. At 0.1 mg/ml ML, viability of PQ-exposed A549 cells was restored by 12.4%, 18.5%, and 48.6% after 24, 48, and 72 h, respectively. ML also reduced production of the intracellular reactive oxygen species (ROS) that were generated by PQ treatment. Further experiments revealed that ML treatment enhanced the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) as well as ARE-GFP reporter activity. ML treatment also effectively increased the expression of NRF2's target genes NAD(P)H dehydrogenase quinone 1 (NQO1) and heme oxygenase 1 (HO-1). Moreover, we found that expression of cytoprotective genes, including glutathione peroxidases (GPXs), superoxide dismutase (SOD1), catalase (CAT), peroxiredoxin 3 (PRDX3), and peroxiredoxin 4 (PRDX4), was greatly enhanced by treatment with ML during PQ exposure. Taken together, the data suggest that treatment of PQ-exposed A549 cells with ML ameliorates cytotoxicity through induction of NRF2 expression and its target genes HO-1, NQO1, and other antioxidant genes. Thus, ML may serve as a functional food applicable to ROS-mediated human diseases.
authors.affiliation: Department of Microbiology, College of Medicine, Soonchunhyang University, Cheonan 31151, Republic of Korea.
authors.forename: Miso
authors.initials: M
authors.lastname: Jeon
authors.affiliation: Department of Microbiology, College of Medicine, Soonchunhyang University, Cheonan 31151, Republic of Korea.|Institute of Tissue Engineering, College of Medicine, Soonchunhyang University, Cheonan 31151, Republic of Korea.
authors.forename: Naimur
authors.initials: N
authors.lastname: Rahman
authors.affiliation: Department of Microbiology, College of Medicine, Soonchunhyang University, Cheonan 31151, Republic of Korea.|Institute of Tissue Engineering, College of Medicine, Soonchunhyang University, Cheonan 31151, Republic of Korea.
authors.forename: Yong-Sik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000975:Antioxidants; D002374:Catalase / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D055951:Functional Food; D017930:Genes, Reporter; D005979:Glutathione Peroxidase / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics; D006540:Herbicides / Q000494:pharmacology*; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010269:Paraquat / Q000494:pharmacology*; D061105:Peroxiredoxin III / Q000235:genetics; D054464:Peroxiredoxins / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics; D014920:Wine
chemical_list: D000975:Antioxidants; D006540:Herbicides; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; C516115:PRDX3 protein, human; C515980:PRDX4 protein, human; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D002374:Catalase; D005979:Glutathione Peroxidase; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D010269:Paraquat
keywords: A549; Antioxidant response element; Makgeolli lees; NRF2; Oxidative stress; Paraquat