Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
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
_version_ 1782322493922476032
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
work_keys_str_mv AT zhangning nrf2signalingcontributestotheneuroprotectiveeffectsofurateagainst6ohdatoxicity
AT shuhaiyang nrf2signalingcontributestotheneuroprotectiveeffectsofurateagainst6ohdatoxicity
AT huangtingting nrf2signalingcontributestotheneuroprotectiveeffectsofurateagainst6ohdatoxicity
AT zhangqilin nrf2signalingcontributestotheneuroprotectiveeffectsofurateagainst6ohdatoxicity
AT lida nrf2signalingcontributestotheneuroprotectiveeffectsofurateagainst6ohdatoxicity
AT zhangguanqun nrf2signalingcontributestotheneuroprotectiveeffectsofurateagainst6ohdatoxicity
AT pengxiaoyan nrf2signalingcontributestotheneuroprotectiveeffectsofurateagainst6ohdatoxicity
AT liuchunfeng nrf2signalingcontributestotheneuroprotectiveeffectsofurateagainst6ohdatoxicity
AT luoweifeng nrf2signalingcontributestotheneuroprotectiveeffectsofurateagainst6ohdatoxicity
AT hulifang nrf2signalingcontributestotheneuroprotectiveeffectsofurateagainst6ohdatoxicity