E-p-Methoxycinnamoyl-α-l-rhamnopyranosyl Ester, a Phenylpropanoid Isolated from Scrophularia buergeriana, Increases Nuclear Factor Erythroid-Derived 2-Related Factor 2 Stability by Inhibiting Ubiquitination in Human Keratinocytes

E-p-Methoxycinnamoyl-α-l-rhamnopyranosyl Ester, a Phenylpropanoid Isolated from Scrophularia buergeriana, Increases Nuclear Factor Erythroid-Derived 2-Related Factor 2 Stability by Inhibiting Ubiquitination in Human Keratinocytes

The nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a key regulator of gene expression during oxidative stress and drug detoxification. Thus, identifying Nrf2 activators to protect from possible cell damage is necessary. In this study, we investigated whether E-p-methoxycinnamoyl-α-l-r...

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Main Authors: Jiwon Jeong, Lilik Duwi Wahyudi, Young-Sam Keum, Heejung Yang, Jung-Hwan Kim
Format: Article
Language:English
Published: MDPI AG 2018-03-01
Series:Molecules
Subjects:
Nrf2
phenylpropanoid
antioxidant
ubiquination
Online Access:http://www.mdpi.com/1420-3049/23/4/768
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spelling doaj-73db44168292498fbb0c67d74e0b24912020-11-24T20:42:03ZengMDPI AGMolecules1420-30492018-03-0123476810.3390/molecules23040768molecules23040768E-p-Methoxycinnamoyl-α-l-rhamnopyranosyl Ester, a Phenylpropanoid Isolated from Scrophularia buergeriana, Increases Nuclear Factor Erythroid-Derived 2-Related Factor 2 Stability by Inhibiting Ubiquitination in Human KeratinocytesJiwon Jeong0Lilik Duwi Wahyudi1Young-Sam Keum2Heejung Yang3Jung-Hwan Kim4Department of Pharmacology, College of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 52727, KoreaDepartment of Pharmacology, College of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 52727, KoreaCollege of Pharmacy, Dongguk University, Goyang 10326, KoreaCollege of Pharmacy, Kangwon National University, Chuncheon 24341, KoreaDepartment of Pharmacology, College of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 52727, KoreaThe nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a key regulator of gene expression during oxidative stress and drug detoxification. Thus, identifying Nrf2 activators to protect from possible cell damage is necessary. In this study, we investigated whether E-p-methoxycinnamoyl-α-l-rhamnopyranosyl ester (MCR), a phenylpropanoid isolated from Scrophularia buergeriana, can activate Nrf2 signaling in human keratinocytes (HaCaT). First, we determined the dose- and time-dependent effects of MCR on the expression and activity of Nrf2. The antioxidant response element-luciferase reporter assay and western blot analysis results showed that MCR markedly induced Nrf2 activity and its protein expression, respectively. Further, MCR increased both the mRNA and protein levels of heme-oxygenase-1, one of the Nrf2 target genes, in the cells. Interestingly, we found that Nrf2 stability was remarkably enhanced by MCR. Furthermore, ubiquitin-dependent proteasomal degradation of Nrf2 was significantly reduced by MCR. Thus, MCR might afford skin protection by enhancing Nrf2 stability or by blocking its proteasomal degradation.http://www.mdpi.com/1420-3049/23/4/768Nrf2phenylpropanoidantioxidantubiquination
collection DOAJ
language English
format Article
sources DOAJ
author Jiwon Jeong
Lilik Duwi Wahyudi
Young-Sam Keum
Heejung Yang
Jung-Hwan Kim
spellingShingle Jiwon Jeong
Lilik Duwi Wahyudi
Young-Sam Keum
Heejung Yang
Jung-Hwan Kim
E-p-Methoxycinnamoyl-α-l-rhamnopyranosyl Ester, a Phenylpropanoid Isolated from Scrophularia buergeriana, Increases Nuclear Factor Erythroid-Derived 2-Related Factor 2 Stability by Inhibiting Ubiquitination in Human Keratinocytes
Molecules
Nrf2
phenylpropanoid
antioxidant
ubiquination
author_facet Jiwon Jeong
Lilik Duwi Wahyudi
Young-Sam Keum
Heejung Yang
Jung-Hwan Kim
author_sort Jiwon Jeong
title E-p-Methoxycinnamoyl-α-l-rhamnopyranosyl Ester, a Phenylpropanoid Isolated from Scrophularia buergeriana, Increases Nuclear Factor Erythroid-Derived 2-Related Factor 2 Stability by Inhibiting Ubiquitination in Human Keratinocytes
title_short E-p-Methoxycinnamoyl-α-l-rhamnopyranosyl Ester, a Phenylpropanoid Isolated from Scrophularia buergeriana, Increases Nuclear Factor Erythroid-Derived 2-Related Factor 2 Stability by Inhibiting Ubiquitination in Human Keratinocytes
title_full E-p-Methoxycinnamoyl-α-l-rhamnopyranosyl Ester, a Phenylpropanoid Isolated from Scrophularia buergeriana, Increases Nuclear Factor Erythroid-Derived 2-Related Factor 2 Stability by Inhibiting Ubiquitination in Human Keratinocytes
title_fullStr E-p-Methoxycinnamoyl-α-l-rhamnopyranosyl Ester, a Phenylpropanoid Isolated from Scrophularia buergeriana, Increases Nuclear Factor Erythroid-Derived 2-Related Factor 2 Stability by Inhibiting Ubiquitination in Human Keratinocytes
title_full_unstemmed E-p-Methoxycinnamoyl-α-l-rhamnopyranosyl Ester, a Phenylpropanoid Isolated from Scrophularia buergeriana, Increases Nuclear Factor Erythroid-Derived 2-Related Factor 2 Stability by Inhibiting Ubiquitination in Human Keratinocytes
title_sort e-p-methoxycinnamoyl-α-l-rhamnopyranosyl ester, a phenylpropanoid isolated from scrophularia buergeriana, increases nuclear factor erythroid-derived 2-related factor 2 stability by inhibiting ubiquitination in human keratinocytes
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2018-03-01
description The nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a key regulator of gene expression during oxidative stress and drug detoxification. Thus, identifying Nrf2 activators to protect from possible cell damage is necessary. In this study, we investigated whether E-p-methoxycinnamoyl-α-l-rhamnopyranosyl ester (MCR), a phenylpropanoid isolated from Scrophularia buergeriana, can activate Nrf2 signaling in human keratinocytes (HaCaT). First, we determined the dose- and time-dependent effects of MCR on the expression and activity of Nrf2. The antioxidant response element-luciferase reporter assay and western blot analysis results showed that MCR markedly induced Nrf2 activity and its protein expression, respectively. Further, MCR increased both the mRNA and protein levels of heme-oxygenase-1, one of the Nrf2 target genes, in the cells. Interestingly, we found that Nrf2 stability was remarkably enhanced by MCR. Furthermore, ubiquitin-dependent proteasomal degradation of Nrf2 was significantly reduced by MCR. Thus, MCR might afford skin protection by enhancing Nrf2 stability or by blocking its proteasomal degradation.
topic Nrf2
phenylpropanoid
antioxidant
ubiquination
url http://www.mdpi.com/1420-3049/23/4/768
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