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Salidroside Protects Dopaminergic Neurons by Preserving Complex I Activity via DJ-1/Nrf2-Mediated Antioxidant Pathway

The pathogenic mechanism of Parkinson's disease (PD) remains to be elucidated; however, mitochondrial dysfunction at the level of complex I and oxidative stress is suggestively involved in the development of PD. In our previous work, salidroside (Sal), an active component extracted from the med...

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Autores principales: Li, Ruru, Wang, Songhai, Li, Tao, Wu, Leitao, Fang, Yan, Feng, Yang, Zhang, Lingling, Chen, Jianzong, Wang, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541949/
https://www.ncbi.nlm.nih.gov/pubmed/31223467
http://dx.doi.org/10.1155/2019/6073496
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author Li, Ruru
Wang, Songhai
Li, Tao
Wu, Leitao
Fang, Yan
Feng, Yang
Zhang, Lingling
Chen, Jianzong
Wang, Xin
author_facet Li, Ruru
Wang, Songhai
Li, Tao
Wu, Leitao
Fang, Yan
Feng, Yang
Zhang, Lingling
Chen, Jianzong
Wang, Xin
author_sort Li, Ruru
collection PubMed
description The pathogenic mechanism of Parkinson's disease (PD) remains to be elucidated; however, mitochondrial dysfunction at the level of complex I and oxidative stress is suggestively involved in the development of PD. In our previous work, salidroside (Sal), an active component extracted from the medicinal plant Rhodiola rosea L., might protect dopaminergic (DA) neurons through modulating ROS–NO-related pathway. However, the mechanism of Sal-induced neuroprotective effects against PD remains poorly understood. Therefore, we further investigated whether Sal plays neuroprotective effects by activating complex I via DJ-1/Nrf2-mediated antioxidant pathway. The results showed that Sal remarkably attenuated MPP(+)/MPTP-induced decline in cell viability, accompanied by decreases in reactive oxygen species (ROS), malondialdehyde (MDA), and 8-hydroxy-deoxyguanosine (8-OHdG) contents and increases in the superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), as well as glutathione (GSH) levels. Furthermore, Sal greatly improved the behavioral performance and prevented the severe reduction of TH-positive neuron numbers in the substantia nigra (SN). Moreover, in comparison with the MPP(+)/MPTP group, Sal increased the nuclear translocation of DJ-1 and Nrf2 and the mitochondrial translocation of DJ-1, accompanied by activating complex I. Furthermore, silencing of DJ-1/Nrf2 inhibited the increase of complex I activity and cell viability elicited by Sal. Together, these results support the neuroprotective effect of Sal against MPP(+)/MPTP-induced DA neurons damage.
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spelling pubmed-65419492019-06-20 Salidroside Protects Dopaminergic Neurons by Preserving Complex I Activity via DJ-1/Nrf2-Mediated Antioxidant Pathway Li, Ruru Wang, Songhai Li, Tao Wu, Leitao Fang, Yan Feng, Yang Zhang, Lingling Chen, Jianzong Wang, Xin Parkinsons Dis Research Article The pathogenic mechanism of Parkinson's disease (PD) remains to be elucidated; however, mitochondrial dysfunction at the level of complex I and oxidative stress is suggestively involved in the development of PD. In our previous work, salidroside (Sal), an active component extracted from the medicinal plant Rhodiola rosea L., might protect dopaminergic (DA) neurons through modulating ROS–NO-related pathway. However, the mechanism of Sal-induced neuroprotective effects against PD remains poorly understood. Therefore, we further investigated whether Sal plays neuroprotective effects by activating complex I via DJ-1/Nrf2-mediated antioxidant pathway. The results showed that Sal remarkably attenuated MPP(+)/MPTP-induced decline in cell viability, accompanied by decreases in reactive oxygen species (ROS), malondialdehyde (MDA), and 8-hydroxy-deoxyguanosine (8-OHdG) contents and increases in the superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), as well as glutathione (GSH) levels. Furthermore, Sal greatly improved the behavioral performance and prevented the severe reduction of TH-positive neuron numbers in the substantia nigra (SN). Moreover, in comparison with the MPP(+)/MPTP group, Sal increased the nuclear translocation of DJ-1 and Nrf2 and the mitochondrial translocation of DJ-1, accompanied by activating complex I. Furthermore, silencing of DJ-1/Nrf2 inhibited the increase of complex I activity and cell viability elicited by Sal. Together, these results support the neuroprotective effect of Sal against MPP(+)/MPTP-induced DA neurons damage. Hindawi 2019-05-16 /pmc/articles/PMC6541949/ /pubmed/31223467 http://dx.doi.org/10.1155/2019/6073496 Text en Copyright © 2019 Ruru Li et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Li, Ruru
Wang, Songhai
Li, Tao
Wu, Leitao
Fang, Yan
Feng, Yang
Zhang, Lingling
Chen, Jianzong
Wang, Xin
Salidroside Protects Dopaminergic Neurons by Preserving Complex I Activity via DJ-1/Nrf2-Mediated Antioxidant Pathway
title Salidroside Protects Dopaminergic Neurons by Preserving Complex I Activity via DJ-1/Nrf2-Mediated Antioxidant Pathway
title_full Salidroside Protects Dopaminergic Neurons by Preserving Complex I Activity via DJ-1/Nrf2-Mediated Antioxidant Pathway
title_fullStr Salidroside Protects Dopaminergic Neurons by Preserving Complex I Activity via DJ-1/Nrf2-Mediated Antioxidant Pathway
title_full_unstemmed Salidroside Protects Dopaminergic Neurons by Preserving Complex I Activity via DJ-1/Nrf2-Mediated Antioxidant Pathway
title_short Salidroside Protects Dopaminergic Neurons by Preserving Complex I Activity via DJ-1/Nrf2-Mediated Antioxidant Pathway
title_sort salidroside protects dopaminergic neurons by preserving complex i activity via dj-1/nrf2-mediated antioxidant pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541949/
https://www.ncbi.nlm.nih.gov/pubmed/31223467
http://dx.doi.org/10.1155/2019/6073496
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