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Morin Induces Heme Oxygenase-1 via ERK-Nrf2 Signaling Pathway

BACKGROUND: Oxidative stress damages to cells or tissues, however, cellular defense systems including heme oxygenase-1 (HO-1) protects them against oxidative stress. Flavonoid compounds can activate cellular defense mechanisms against oxidative stress and it can reduce cell damages. In the present s...

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Autores principales: Park, Ji Young, Kang, Kyoung Ah, Kim, Ki Cheon, Cha, Ji Won, Kim, Eun Hee, Hyun, Jin Won
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society of Cancer Prevention 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189466/
https://www.ncbi.nlm.nih.gov/pubmed/25337552
http://dx.doi.org/10.15430/JCP.2013.18.3.249
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author Park, Ji Young
Kang, Kyoung Ah
Kim, Ki Cheon
Cha, Ji Won
Kim, Eun Hee
Hyun, Jin Won
author_facet Park, Ji Young
Kang, Kyoung Ah
Kim, Ki Cheon
Cha, Ji Won
Kim, Eun Hee
Hyun, Jin Won
author_sort Park, Ji Young
collection PubMed
description BACKGROUND: Oxidative stress damages to cells or tissues, however, cellular defense systems including heme oxygenase-1 (HO-1) protects them against oxidative stress. Flavonoid compounds can activate cellular defense mechanisms against oxidative stress and it can reduce cell damages. In the present study, the cytoprotective effects of morin (3,5,7,2’,4’-pentahydroxyflavone), in terms of HO-1 enzyme, against the oxidative stress and its involved mechanisms was elucidated. METHODS: RT-PCR and western blot analysis were assessed to detect the mRNA and protein expression, respectively. Cell viability was measured by using MTT test. The immunocytochemistry was performed to define location of target protein. Electrophoretic mobility shift assay performed to measure transcription factor-promoter site binding activity. RESULTS: Morin elevated mRNA and protein levels of HO-1 in human lens epithelial cells (HLE-B3). HO-1 inhibitor ZnPP attenuated the protective effect of morin against H(2)O(2)-induced cytotoxicity. Morin increased the protein level of transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which up-regulates HO-1 expression by binding to the antioxidant response element (ARE) within the HO-1 gene promoter. Moreover, morin induced the translocation of Nrf2 from the cytosol into the nucleus. Morin activated extracellular-regulated kinase (ERK), while ERK inhibitor attenuated morin-enhanced Nrf2 and HO-1 expression. CONCLUSIONS: Morin activates ERK-Nrf2 signaling cascades in HLE-B3 cells, leading to the up-regulation of HO-1 and cytoprotection against oxidative stress.
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spelling pubmed-41894662014-10-21 Morin Induces Heme Oxygenase-1 via ERK-Nrf2 Signaling Pathway Park, Ji Young Kang, Kyoung Ah Kim, Ki Cheon Cha, Ji Won Kim, Eun Hee Hyun, Jin Won J Cancer Prev Original Article BACKGROUND: Oxidative stress damages to cells or tissues, however, cellular defense systems including heme oxygenase-1 (HO-1) protects them against oxidative stress. Flavonoid compounds can activate cellular defense mechanisms against oxidative stress and it can reduce cell damages. In the present study, the cytoprotective effects of morin (3,5,7,2’,4’-pentahydroxyflavone), in terms of HO-1 enzyme, against the oxidative stress and its involved mechanisms was elucidated. METHODS: RT-PCR and western blot analysis were assessed to detect the mRNA and protein expression, respectively. Cell viability was measured by using MTT test. The immunocytochemistry was performed to define location of target protein. Electrophoretic mobility shift assay performed to measure transcription factor-promoter site binding activity. RESULTS: Morin elevated mRNA and protein levels of HO-1 in human lens epithelial cells (HLE-B3). HO-1 inhibitor ZnPP attenuated the protective effect of morin against H(2)O(2)-induced cytotoxicity. Morin increased the protein level of transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which up-regulates HO-1 expression by binding to the antioxidant response element (ARE) within the HO-1 gene promoter. Moreover, morin induced the translocation of Nrf2 from the cytosol into the nucleus. Morin activated extracellular-regulated kinase (ERK), while ERK inhibitor attenuated morin-enhanced Nrf2 and HO-1 expression. CONCLUSIONS: Morin activates ERK-Nrf2 signaling cascades in HLE-B3 cells, leading to the up-regulation of HO-1 and cytoprotection against oxidative stress. Korean Society of Cancer Prevention 2013-09 /pmc/articles/PMC4189466/ /pubmed/25337552 http://dx.doi.org/10.15430/JCP.2013.18.3.249 Text en Copyright © 2013 Korean Society of Cancer Prevention This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Park, Ji Young
Kang, Kyoung Ah
Kim, Ki Cheon
Cha, Ji Won
Kim, Eun Hee
Hyun, Jin Won
Morin Induces Heme Oxygenase-1 via ERK-Nrf2 Signaling Pathway
title Morin Induces Heme Oxygenase-1 via ERK-Nrf2 Signaling Pathway
title_full Morin Induces Heme Oxygenase-1 via ERK-Nrf2 Signaling Pathway
title_fullStr Morin Induces Heme Oxygenase-1 via ERK-Nrf2 Signaling Pathway
title_full_unstemmed Morin Induces Heme Oxygenase-1 via ERK-Nrf2 Signaling Pathway
title_short Morin Induces Heme Oxygenase-1 via ERK-Nrf2 Signaling Pathway
title_sort morin induces heme oxygenase-1 via erk-nrf2 signaling pathway
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189466/
https://www.ncbi.nlm.nih.gov/pubmed/25337552
http://dx.doi.org/10.15430/JCP.2013.18.3.249
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