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.

Ganoderic Acid D Protects Human Amniotic Mesenchymal Stem Cells against Oxidative Stress-Induced Senescence through the PERK/NRF2 Signaling Pathway

“…Therefore, two inhibitors could individually result in an increase in ROS levels and β-galactosidase and the diminished differentiation potential of hAMSCs in the GA-D treatment group. Consistent with the results of a previous study [53], our results showed that GA-D activated the expression of PERK, thereby promoting the intranuclear transfer of NRF2 to enhance the expression of PRDX3. Additionally, the activity of NRF2 was regulated by PERK, which activated NRF2 to reduce cell cycle arrest caused by oxidative stress [31].…”

“…After GA-D pretreatment, the phosphorylation level of PERK was upregulated ( Figure 5(e)), which might have mediated the occurrence of UPR to reduce ER stress. Meanwhile, p-PERK promoted the expression of NRF2 and nuclear transfer (Figures 5(c) and 5(d)) and finally triggered an increase in the transcription of downstream genes of NRF2, including PRDX3, HO-1, and quinine oxidoreductase 1 (NQO1) [53]. Consequently, hAMSC senescence was mitigated by decreased accumulation of ROS.…”

3,4-Dihydroxybenzalactone Suppresses Human Non-Small Cell Lung Carcinoma Cells Metastasis via Suppression of Epithelial to Mesenchymal Transition, ROS-Mediated PI3K/AKT/MAPK/MMP and NFκB Signaling Pathways

“…Normal intracellular metabolism and environmental stimuli can cause ROS generation. Detoxification enzymes—include HO-1, SOD, catalase, and GPx—can neutralize these oxidative stresses [ 40 ]. SOD is an enzyme that can convert the superoxide radical to hydrogen peroxide.…”

Methyl gallate, a potent antioxidant inhibits mouse and human adipocyte differentiation and oxidative stress in adipocytes through impairment of mitotic clonal expansion

“…It has been reported that reactive oxygen species (ROS) can accelerate MCE and promote adipocyte differentiation, and ROS levels increased especially strongly during MCE [33,34]. Nrf2 is a key regulator of cellular defense against oxidative stress caused by ROS and promotes expression of cytoprotective enzymes, such as HO-1, NQO1, SOD1, CAT, PRDX3, and PRDX4 [35,36]. We confirmed that MG reduces intracellular ROS to a lesser extent than the potent antioxidant NAC does, mostly during MCE and during terminal differentiation by activating Nrf2, HO-1 and PRDX3 expression which suggest that MG-mediated inhibition of MCE may govern by its antioxidant action.…”