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Nrf2 Signaling Contributes to the Neuroprotective Effects of Urate against 6-OHDA Toxicity
BACKGROUND: Mounting evidence shows that urate may become a biomarker of Parkinson's disease (PD) diagnosis and prognosis and a neuroprotectant candidate for PD therapy. However, the cellular and molecular mechanisms underlying its neuroprotective actions remain poorly understood. RESULTS: In t...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069024/ https://www.ncbi.nlm.nih.gov/pubmed/24959672 http://dx.doi.org/10.1371/journal.pone.0100286 |
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author | Zhang, Ning Shu, Hai-Yang Huang, Tingting Zhang, Qi-Lin Li, Da Zhang, Guan-Qun Peng, Xiao-Yan Liu, Chun-Feng Luo, Wei-Feng Hu, Li-Fang |
author_facet | Zhang, Ning Shu, Hai-Yang Huang, Tingting Zhang, Qi-Lin Li, Da Zhang, Guan-Qun Peng, Xiao-Yan Liu, Chun-Feng Luo, Wei-Feng Hu, Li-Fang |
author_sort | Zhang, Ning |
collection | PubMed |
description | BACKGROUND: Mounting evidence shows that urate may become a biomarker of Parkinson's disease (PD) diagnosis and prognosis and a neuroprotectant candidate for PD therapy. However, the cellular and molecular mechanisms underlying its neuroprotective actions remain poorly understood. RESULTS: In this study, we showed that urate pretreatment protected dopaminergic cell line (SH-SY5Y and MES23.5) against 6-hydroxydopamine (6-OHDA)- and hydrogen peroxide- induced cell damage. Urate was found to be accumulated into SH-SY5Y cells after 30 min treatment. Moreover, urate induced NF-E2-related factor 2 (Nrf2) accumulation by inhibiting its ubiquitinationa and degradation, and also promoted its nuclear translocation; however, it did not modulate Nrf2 mRNA level or Kelch-like ECH-associated protein 1 (Keap1) expression. In addition, urate markedly up-regulated the transcription and protein expression of γ-glutamate-cysteine ligase catalytic subunit (γ-GCLC) and heme oxygenase-1 (HO-1), both of which are controlled by Nrf2 activity. Furthermore, Nrf2 knockdown by siRNA abolished the intracellular glutathione augmentation and the protection exerted by urate pretreatment. CONCLUSION: Our findings demonstrated that urate treatment may result in Nrf2-targeted anti-oxidant genes transcription and expression by reducing Nrf2 ubiquitination and degradation and promoting its nuclear translocation, and thus offer neuroprotection on dopaminergic cells against oxidative stresses. |
format | Online Article Text |
id | pubmed-4069024 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40690242014-06-27 Nrf2 Signaling Contributes to the Neuroprotective Effects of Urate against 6-OHDA Toxicity Zhang, Ning Shu, Hai-Yang Huang, Tingting Zhang, Qi-Lin Li, Da Zhang, Guan-Qun Peng, Xiao-Yan Liu, Chun-Feng Luo, Wei-Feng Hu, Li-Fang PLoS One Research Article BACKGROUND: Mounting evidence shows that urate may become a biomarker of Parkinson's disease (PD) diagnosis and prognosis and a neuroprotectant candidate for PD therapy. However, the cellular and molecular mechanisms underlying its neuroprotective actions remain poorly understood. RESULTS: In this study, we showed that urate pretreatment protected dopaminergic cell line (SH-SY5Y and MES23.5) against 6-hydroxydopamine (6-OHDA)- and hydrogen peroxide- induced cell damage. Urate was found to be accumulated into SH-SY5Y cells after 30 min treatment. Moreover, urate induced NF-E2-related factor 2 (Nrf2) accumulation by inhibiting its ubiquitinationa and degradation, and also promoted its nuclear translocation; however, it did not modulate Nrf2 mRNA level or Kelch-like ECH-associated protein 1 (Keap1) expression. In addition, urate markedly up-regulated the transcription and protein expression of γ-glutamate-cysteine ligase catalytic subunit (γ-GCLC) and heme oxygenase-1 (HO-1), both of which are controlled by Nrf2 activity. Furthermore, Nrf2 knockdown by siRNA abolished the intracellular glutathione augmentation and the protection exerted by urate pretreatment. CONCLUSION: Our findings demonstrated that urate treatment may result in Nrf2-targeted anti-oxidant genes transcription and expression by reducing Nrf2 ubiquitination and degradation and promoting its nuclear translocation, and thus offer neuroprotection on dopaminergic cells against oxidative stresses. Public Library of Science 2014-06-24 /pmc/articles/PMC4069024/ /pubmed/24959672 http://dx.doi.org/10.1371/journal.pone.0100286 Text en © 2014 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Zhang, Ning Shu, Hai-Yang Huang, Tingting Zhang, Qi-Lin Li, Da Zhang, Guan-Qun Peng, Xiao-Yan Liu, Chun-Feng Luo, Wei-Feng Hu, Li-Fang Nrf2 Signaling Contributes to the Neuroprotective Effects of Urate against 6-OHDA Toxicity |
title | Nrf2 Signaling Contributes to the Neuroprotective Effects of Urate against 6-OHDA Toxicity |
title_full | Nrf2 Signaling Contributes to the Neuroprotective Effects of Urate against 6-OHDA Toxicity |
title_fullStr | Nrf2 Signaling Contributes to the Neuroprotective Effects of Urate against 6-OHDA Toxicity |
title_full_unstemmed | Nrf2 Signaling Contributes to the Neuroprotective Effects of Urate against 6-OHDA Toxicity |
title_short | Nrf2 Signaling Contributes to the Neuroprotective Effects of Urate against 6-OHDA Toxicity |
title_sort | nrf2 signaling contributes to the neuroprotective effects of urate against 6-ohda toxicity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069024/ https://www.ncbi.nlm.nih.gov/pubmed/24959672 http://dx.doi.org/10.1371/journal.pone.0100286 |
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