Protective Effects of Querectin against MPP+-Induced Dopaminergic Neurons Injury via the Nrf2 Signaling Pathway
Background: Parkinson’s disease (PD) is a common selective and progressive neurodegenerative disorder of nigrostriatal dopaminergic (DA) neurons. Quercetin is a bioflavonoid with antioxidant, anti-inflammatory, anti-aging and anti-cancer properties. However, the exact mechanism by which quercetin ex...
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| Format: | Article |
| Language: | English |
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IMR Press
2023-03-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/28/3/10.31083/j.fbl2803042 |
| _version_ | 1797853511102234624 |
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| author | Yanyan Jiang Guangming Xie Aydos Alimujiang Hongrong Xie Weiting Yang Feng Yin Dongya Huang |
| author_facet | Yanyan Jiang Guangming Xie Aydos Alimujiang Hongrong Xie Weiting Yang Feng Yin Dongya Huang |
| author_sort | Yanyan Jiang |
| collection | DOAJ |
| description | Background: Parkinson’s disease (PD) is a common selective and progressive neurodegenerative disorder of nigrostriatal dopaminergic (DA) neurons. Quercetin is a bioflavonoid with antioxidant, anti-inflammatory, anti-aging and anti-cancer properties. However, the exact mechanism by which quercetin exerts its protective effect on DAergic neurons remains unclear. Purpose: To investigate the underlying molecular mechanism of quercetin’s protective effect on DA neurons using 1-methyl-4-phenylpyridinium (MPP+)-induced PD ferroptosis model in vitro. Methods: MPP+ was used to induce cytotoxicity in SH-SY5Y/primary neurons. Cell viability and apoptosis were assessed by CCK-8 assay and flow cytometry. The expression levels of ferroptosis-related proteins (NCOA4, SLC7A11, Nrf2, and GPX4) were determined by Western blotting. Malondialdehyde (MDA), iron, and GPX4 levels were assesed using corresponding assay kits. Lipid peroxidation was assessed by C11-BODIPY staining. Results: In the MPP+-induced ferroptosis model of SH-SY5Y cells, the expressions of SLC7A11 and GPX4 were inhibited, and the expression of NCOA4 protein was increased, causing the overproduction of MDA and lipid peroxidation. Quercetin can reduce the above changes caused by MPP+, that is, reduce the protein expression of NCOA4 in SH-SY5Y cells, increase SLC7A11 and GPX4 partially inhibited by MPP+, and reduce MDA overproduction and lipid peroxidation to protect DA neurons. Nrf2 inhibitor ML385 could inhibit quercetin-induced increase of GPX4 and SLC7A11 protein expression, indicating that the protective effect of quercetin was mediated through Nrf2. Conclusions: The results of this study suggest that quercetin regulates ferroptosis through Nrf2-dependent signaling pathways, thereby inhibiting MPP+-induced neurotoxicity in SH-SY5Y/primary neurons. |
| first_indexed | 2024-04-09T19:50:46Z |
| format | Article |
| id | doaj.art-4f9103ef3f1046b296e0314d43316561 |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-04-09T19:50:46Z |
| publishDate | 2023-03-01 |
| publisher | IMR Press |
| record_format | Article |
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| spelling | doaj.art-4f9103ef3f1046b296e0314d433165612023-04-03T05:52:10ZengIMR PressFrontiers in Bioscience-Landmark2768-67012023-03-012834210.31083/j.fbl2803042S2768-6701(22)00749-3Protective Effects of Querectin against MPP+-Induced Dopaminergic Neurons Injury via the Nrf2 Signaling PathwayYanyan Jiang0Guangming Xie1Aydos Alimujiang2Hongrong Xie3Weiting Yang4Feng Yin5Dongya Huang6Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, 200120 Shanghai, ChinaSchool of Medicine, Tongji University, 200092 Shanghai, ChinaDepartment of Neurology, Shanghai East Hospital, Tongji University School of Medicine, 200120 Shanghai, ChinaDepartment of Neurology, Shanghai East Hospital, Tongji University School of Medicine, 200120 Shanghai, ChinaDepartment of Neurology, Shanghai East Hospital, Tongji University School of Medicine, 200120 Shanghai, ChinaDepartment of Joint Surgery & Shanghai Institute of Stem Cell Research and Clinical Translation and Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, 200120 Shanghai, ChinaDepartment of Neurology, Shanghai East Hospital, Tongji University School of Medicine, 200120 Shanghai, ChinaBackground: Parkinson’s disease (PD) is a common selective and progressive neurodegenerative disorder of nigrostriatal dopaminergic (DA) neurons. Quercetin is a bioflavonoid with antioxidant, anti-inflammatory, anti-aging and anti-cancer properties. However, the exact mechanism by which quercetin exerts its protective effect on DAergic neurons remains unclear. Purpose: To investigate the underlying molecular mechanism of quercetin’s protective effect on DA neurons using 1-methyl-4-phenylpyridinium (MPP+)-induced PD ferroptosis model in vitro. Methods: MPP+ was used to induce cytotoxicity in SH-SY5Y/primary neurons. Cell viability and apoptosis were assessed by CCK-8 assay and flow cytometry. The expression levels of ferroptosis-related proteins (NCOA4, SLC7A11, Nrf2, and GPX4) were determined by Western blotting. Malondialdehyde (MDA), iron, and GPX4 levels were assesed using corresponding assay kits. Lipid peroxidation was assessed by C11-BODIPY staining. Results: In the MPP+-induced ferroptosis model of SH-SY5Y cells, the expressions of SLC7A11 and GPX4 were inhibited, and the expression of NCOA4 protein was increased, causing the overproduction of MDA and lipid peroxidation. Quercetin can reduce the above changes caused by MPP+, that is, reduce the protein expression of NCOA4 in SH-SY5Y cells, increase SLC7A11 and GPX4 partially inhibited by MPP+, and reduce MDA overproduction and lipid peroxidation to protect DA neurons. Nrf2 inhibitor ML385 could inhibit quercetin-induced increase of GPX4 and SLC7A11 protein expression, indicating that the protective effect of quercetin was mediated through Nrf2. Conclusions: The results of this study suggest that quercetin regulates ferroptosis through Nrf2-dependent signaling pathways, thereby inhibiting MPP+-induced neurotoxicity in SH-SY5Y/primary neurons.https://www.imrpress.com/journal/FBL/28/3/10.31083/j.fbl2803042parkinson's diseasequercetinnrf2-dependent signaling pathwayferroptosis |
| spellingShingle | Yanyan Jiang Guangming Xie Aydos Alimujiang Hongrong Xie Weiting Yang Feng Yin Dongya Huang Protective Effects of Querectin against MPP+-Induced Dopaminergic Neurons Injury via the Nrf2 Signaling Pathway Frontiers in Bioscience-Landmark parkinson's disease quercetin nrf2-dependent signaling pathway ferroptosis |
| title | Protective Effects of Querectin against MPP+-Induced Dopaminergic Neurons Injury via the Nrf2 Signaling Pathway |
| title_full | Protective Effects of Querectin against MPP+-Induced Dopaminergic Neurons Injury via the Nrf2 Signaling Pathway |
| title_fullStr | Protective Effects of Querectin against MPP+-Induced Dopaminergic Neurons Injury via the Nrf2 Signaling Pathway |
| title_full_unstemmed | Protective Effects of Querectin against MPP+-Induced Dopaminergic Neurons Injury via the Nrf2 Signaling Pathway |
| title_short | Protective Effects of Querectin against MPP+-Induced Dopaminergic Neurons Injury via the Nrf2 Signaling Pathway |
| title_sort | protective effects of querectin against mpp induced dopaminergic neurons injury via the nrf2 signaling pathway |
| topic | parkinson's disease quercetin nrf2-dependent signaling pathway ferroptosis |
| url | https://www.imrpress.com/journal/FBL/28/3/10.31083/j.fbl2803042 |
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