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Neuroprotective effects of urolithin A on H(2)O(2)-induced oxidative stress-mediated apoptosis in SK-N-MC cells
BACKGROUND/OBJECTIVES: Oxidative stress causes cell damage and death, which contribute to the pathogenesis of neurodegenerative diseases. Urolithin A (UA), a gut microbial-derived metabolite of ellagitannins and ellagic acid, has high bioavailability and various health benefits such as antioxidant a...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Nutrition Society and the Korean Society of Community Nutrition
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997143/ https://www.ncbi.nlm.nih.gov/pubmed/32042368 http://dx.doi.org/10.4162/nrp.2020.14.1.3 |
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author | Kim, Kkot Byeol Lee, Seonah Kim, Jung Hee |
author_facet | Kim, Kkot Byeol Lee, Seonah Kim, Jung Hee |
author_sort | Kim, Kkot Byeol |
collection | PubMed |
description | BACKGROUND/OBJECTIVES: Oxidative stress causes cell damage and death, which contribute to the pathogenesis of neurodegenerative diseases. Urolithin A (UA), a gut microbial-derived metabolite of ellagitannins and ellagic acid, has high bioavailability and various health benefits such as antioxidant and anti-inflammatory effects. However, it is unknown whether it has protective effects against oxidative stress-induced cell death. We investigated whether UA ameliorates H(2)O(2)-induced neuronal cell death. MATERIALS/METHODS: We induced oxidative damage with 300 µM H(2)O(2) after UA pretreatment at concentrations of 1.25, 2.5, and 5 µM in SK-N-MC cells. Cytotoxicity and cell viability were determined using the CCK-8 assay. The formation of reactive oxygen species (ROS) was measured using a 2,7-dichlorofluorescein diacetate assay. Hoechst 33342 staining was used to characterize morphological changes in apoptotic cells. The expressions of apoptosis proteins were measured using Western blotting. RESULTS: UA significantly increased cell viability and decreased intracellular ROS production in a dose-dependent manner in SK-N-MC cells. It also decreased the Bax/Bcl-2 ratio and the expressions of cytochrome c, cleaved caspase-9, cleaved caspase-3, and cleaved PARP. In addition, it suppressed the phosphorylation of the p38 mitogen-activated protein kinase (MAPK) pathway. CONCLUSIONS: UA attenuates oxidative stress-induced apoptosis via inhibiting the mitochondrial-related apoptosis pathway and modulating the p38 MAPK pathway, suggesting that it may be an effective neuroprotective agent. |
format | Online Article Text |
id | pubmed-6997143 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Korean Nutrition Society and the Korean Society of Community Nutrition |
record_format | MEDLINE/PubMed |
spelling | pubmed-69971432020-02-10 Neuroprotective effects of urolithin A on H(2)O(2)-induced oxidative stress-mediated apoptosis in SK-N-MC cells Kim, Kkot Byeol Lee, Seonah Kim, Jung Hee Nutr Res Pract Original Research BACKGROUND/OBJECTIVES: Oxidative stress causes cell damage and death, which contribute to the pathogenesis of neurodegenerative diseases. Urolithin A (UA), a gut microbial-derived metabolite of ellagitannins and ellagic acid, has high bioavailability and various health benefits such as antioxidant and anti-inflammatory effects. However, it is unknown whether it has protective effects against oxidative stress-induced cell death. We investigated whether UA ameliorates H(2)O(2)-induced neuronal cell death. MATERIALS/METHODS: We induced oxidative damage with 300 µM H(2)O(2) after UA pretreatment at concentrations of 1.25, 2.5, and 5 µM in SK-N-MC cells. Cytotoxicity and cell viability were determined using the CCK-8 assay. The formation of reactive oxygen species (ROS) was measured using a 2,7-dichlorofluorescein diacetate assay. Hoechst 33342 staining was used to characterize morphological changes in apoptotic cells. The expressions of apoptosis proteins were measured using Western blotting. RESULTS: UA significantly increased cell viability and decreased intracellular ROS production in a dose-dependent manner in SK-N-MC cells. It also decreased the Bax/Bcl-2 ratio and the expressions of cytochrome c, cleaved caspase-9, cleaved caspase-3, and cleaved PARP. In addition, it suppressed the phosphorylation of the p38 mitogen-activated protein kinase (MAPK) pathway. CONCLUSIONS: UA attenuates oxidative stress-induced apoptosis via inhibiting the mitochondrial-related apoptosis pathway and modulating the p38 MAPK pathway, suggesting that it may be an effective neuroprotective agent. The Korean Nutrition Society and the Korean Society of Community Nutrition 2020-02 2019-10-18 /pmc/articles/PMC6997143/ /pubmed/32042368 http://dx.doi.org/10.4162/nrp.2020.14.1.3 Text en ©2020 The Korean Nutrition Society and the Korean Society of Community Nutrition http://creativecommons.org/licenses/by-nc/3.0/ 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 Research Kim, Kkot Byeol Lee, Seonah Kim, Jung Hee Neuroprotective effects of urolithin A on H(2)O(2)-induced oxidative stress-mediated apoptosis in SK-N-MC cells |
title | Neuroprotective effects of urolithin A on H(2)O(2)-induced oxidative stress-mediated apoptosis in SK-N-MC cells |
title_full | Neuroprotective effects of urolithin A on H(2)O(2)-induced oxidative stress-mediated apoptosis in SK-N-MC cells |
title_fullStr | Neuroprotective effects of urolithin A on H(2)O(2)-induced oxidative stress-mediated apoptosis in SK-N-MC cells |
title_full_unstemmed | Neuroprotective effects of urolithin A on H(2)O(2)-induced oxidative stress-mediated apoptosis in SK-N-MC cells |
title_short | Neuroprotective effects of urolithin A on H(2)O(2)-induced oxidative stress-mediated apoptosis in SK-N-MC cells |
title_sort | neuroprotective effects of urolithin a on h(2)o(2)-induced oxidative stress-mediated apoptosis in sk-n-mc cells |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997143/ https://www.ncbi.nlm.nih.gov/pubmed/32042368 http://dx.doi.org/10.4162/nrp.2020.14.1.3 |
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