Role of nuclear factor E2-related factor 2 (Nrf2) in epidermal differentiation

Lee, Young; Shin, Jung-Hye; Jang, Sunhyae; Choi, Dae Eun; Seo, Min-Seok; Kim, Hyeong-Rae; Sohn, Kyung-Ah; Im, Myung; Seo, Young‐Joon; Lee, Jeung‐Hoon; Kim, Chang Deok

doi:10.1007/s00403-014-1470-x

Cited by 25 publications

(29 citation statements)

References 13 publications

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“…We explored the possible mechanisms underlying these effects. Since Nrf2 has recently been mentioned as an important regulator of the oxidative response as well as of differentiation of keratinocytes (Beyer, et al, 2007;Lee, et al, 2014), we determined whether MMF increased Nrf2 levels by using a 200 mM concentration of MMF as was done in several other systems (Nibbering, et al, 1993;Thio, et al, 1994;Garcia-Caballero et al, 2011), as well as a 300 mM dose that we had previously shown to inhibit inflammatory mediator production in keratinocytes (Helwa et al, 2015). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Anti-Psoriatic Drug Monomethylfumarate Increases Nuclear Factor Erythroid 2-Related Factor 2 Levels and Induces Aquaporin-3 mRNA and Protein Expression

Helwa

Choudhary

Chen

et al. 2017

J Pharmacol Exp Ther

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Oxidative stress contributes to inflammatory skin diseases, including psoriasis. Monomethylfumarate (MMF) is an antipsoriatic agent with a poorly understood mechanism of action. In other cell types MMF increases the expression of nuclear factor erythroid-derived 2-like 2 (Nrf2), a transcription factor that regulates cellular antioxidant responses, to reduce oxidative stress like that observed in inflammatory disorders such as multiple sclerosis. We tested the hypothesis that MMF enhances Nrf2 activity in keratinocytes, thereby improving their capacity to counteract environmental stresses. We used Western analysis, immunofluorescence, and real-time quantitative reverse-transcription polymerase chain reaction to examine the effect of MMF on the expression of Nrf2 and its targets. We also measured intracellular reactive oxygen species (ROS) levels following MMF treatment. Our data show that MMF increased total and nuclear Nrf2 levels in primary mouse keratinocytes and enhanced mRNA expression of several Nrf2-downstream effectors, including heme oxygenase-1 and peroxiredoxin-6. Moreover, MMF treatment attenuated the generation of ROS following hydrogen peroxide treatment. On the other hand, the expression and membranous localization of aquaporin-3 (AQP3), a glycerol channel implicated in keratinocyte differentiation, was stimulated by MMF, which also enhanced keratinocyte glycerol uptake. The Nrf2 activator sulforaphane also increased AQP3 levels, suggesting that AQP3 expression may be regulated by Nrf2. We show for the first time that MMF stimulates Nrf2 and AQP3 expression and function/activity in keratinocytes. This effect may account, in part, for the previously observed ability of MMF to inhibit proliferation and inflammatory mediator production and promote differentiation in keratinocytes and to treat psoriasis.

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Section: Resultsmentioning

confidence: 99%

Anti-Psoriatic Drug Monomethylfumarate Increases Nuclear Factor Erythroid 2-Related Factor 2 Levels and Induces Aquaporin-3 mRNA and Protein Expression

Helwa

Choudhary

Chen

et al. 2017

J Pharmacol Exp Ther

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“…Nrf2 has two effects, firstly, promotes regeneration and expression of antioxidant enzymes [61], and secondly, it can perpetuate the survival of damaged cells by ROS generated during aerobic metabolism, and the respiratory burst of the immune cell system, increasing the resistance to apoptosis of cells in culture under UV ray [62]. Nrf2 can be activated by the sulforane (obtained from broccoli and Brussels sprouts) [8].…”

Section: Skinmentioning

confidence: 99%

Possible Role of Nrf2 in Oxidative and Inflammatory Processes During Menopause

Mendoza¹,

Zamarripa²,

Hernández³

et al. 2016

A Master Regulator of Oxidative Stress - The Transcription Factor Nrf2

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The increase in life expectancy leads to the possibility of development chronic diseases, from special physiological conditions as occurs in the menopause, which is defined as the permanent cessation of ovulation, marked by the end of menstruation. It has been related to decreased ovarian function that occurs around an age of 45 years. This event involves the reduction in estrogen production and may contribute to the development of chronic-degenerative diseases. Many diseases developed during menopause have been associated with oxidative stress, such as osteoporosis, hot flushes, cognitive impairment, insulin resistance, dry skin, obesity, and cardiovascular events. The knowledge about the participation of Nrf2 in diseases that occur during menopause is very limited. Here, only diseases such as osteoporosis, cardiovascular diseases and dry skin, which are present during menopause and its later stages have been described. The Nrf2 pathway involves the participation of PI3K/Akt, MAPK, and eNOS, which act as mediators for cytoprotection and antioxidation. Compounds such as equol, fitoestrogens, alkyl cathecols, or curcumin could be offered as options to antioxidant treatment, added the fact that they are present in fruits and vegetables which are rich in vitamins, minerals and calcium, thus including all the required nutrients for an adequate nutrition.

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“…It has been shown that nuclear factor E2-related factor2 (Nrf2) is involved in the protective effect of Hyp on hepatocytes (22,23). Studies have shown that Nrf2 and its cytoplasmic protein, kelch-like ECH-associated protein 1 (Keap1), are central regulators of cell antioxidant responses (24,25). Nrf2 regulates the expression of antioxidant proteins and phase II detoxification enzymes by interacting with a cis-acting transcriptional regulatory element, designated as antioxidant response element or electrophile response element (EpRE).…”

Section: Introductionmentioning

confidence: 99%

Hyperoside protects human kidney‑2 cells against oxidative damage induced by oxalic acid

Chen

et al. 2018

Mol Med Report

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The majority of renal calculi (kidney stones) are calcium stones. Oxidative damage to renal tubular epithelial cells induced by reactive oxygen species (ROS) is the predominant cause of calcium oxalate stone formation. Hyperoside (Hyp) is a flavonol glycoside extracted from medicinal plants and appears to exhibit potent antioxidant activity in various cells. The aim of the present study was to investigate the protective effect of Hyp on renal cells exposed to oxidative stress simulated by oxalic acid (OA), and to determine whether the underlying mechanism involves the nuclear factor E2‑related factor2 (Nrf2)‑antioxidative response element signaling pathway. The study determined the indicators of high oxidative stress, including ROS and hydrogen peroxide (H2O2) in human kidney‑2 cells and the results demonstrated that the levels of ROS, as evaluated by flow cytometry, and H2O2 were significantly increased following treatment with OA (5 mmol/l) for 24 h (OA group), compared with those in the untreated control group. The increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in these cells explained this observation, as it is a major source of ROS. The results demonstrated that, in the OA group, the adhesion of calcium oxalate crystals and lactate dehydrogenase (LDH) were significantly increased, and MTT assay demonstrated that cell viability was inhibited, compared with the control, which indicated that severe injury of cells was induced by OA. However, when the cells were pre‑treated with Hyp prior to treatment with OA (drug group), the levels of ROS and H2O2, and the activities of NADPH oxidase and LD were increased, and the adhesion of calcium oxalate crystals to cells was reduced, compared with the OA group. Western blot analysis and reverse transcription‑quantitative polymerase chain reaction demonstrated that the protein and mRNA expression levels of Nrf2, heme oxygenase‑1 (HO‑1) and NAD(P)H: quinineoxidoreductase 1 (NQO1) in the Hyp groups were significantly increased, compared with those in the OA group, with the exception of Nrf2 mRNA. These results suggested that Hyp had a marked protective effect on renal cells against the oxidative damage and cytotoxicity simulated by OA. This is the first report, to the best of our knowledge, demonstrating that the ability of Hyp to enhance the endogenous functions of antioxidation and detoxification in cells may involve the Nrf2/HO‑1/NQO1 pathway.

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Role of nuclear factor E2-related factor 2 (Nrf2) in epidermal differentiation

Cited by 25 publications

References 13 publications

Anti-Psoriatic Drug Monomethylfumarate Increases Nuclear Factor Erythroid 2-Related Factor 2 Levels and Induces Aquaporin-3 mRNA and Protein Expression

Anti-Psoriatic Drug Monomethylfumarate Increases Nuclear Factor Erythroid 2-Related Factor 2 Levels and Induces Aquaporin-3 mRNA and Protein Expression

Possible Role of Nrf2 in Oxidative and Inflammatory Processes During Menopause

Hyperoside protects human kidney‑2 cells against oxidative damage induced by oxalic acid

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