Mitochondrial Effects of PGC-1alpha Silencing in MPP+ Treated Human SH-SY5Y Neuroblastoma Cells
The dopaminergic neuron degeneration and loss that occurs in Parkinson’s disease (PD) has been tightly linked to mitochondrial dysfunction. Although the aged-related cause of the mitochondrial defect observed in PD patients remains unclear, nuclear genes are of potential importance to mitochondrial...
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Frontiers Media S.A.
2017-05-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00164/full |
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| author | Qinyong Ye Qinyong Ye Chun Chen Erwang Si Yousheng Cai Juhua Wang Wanling Huang Dongzhu Li Yingqing Wang Xiaochun Chen Xiaochun Chen |
| author_facet | Qinyong Ye Qinyong Ye Chun Chen Erwang Si Yousheng Cai Juhua Wang Wanling Huang Dongzhu Li Yingqing Wang Xiaochun Chen Xiaochun Chen |
| author_sort | Qinyong Ye |
| collection | DOAJ |
| description | The dopaminergic neuron degeneration and loss that occurs in Parkinson’s disease (PD) has been tightly linked to mitochondrial dysfunction. Although the aged-related cause of the mitochondrial defect observed in PD patients remains unclear, nuclear genes are of potential importance to mitochondrial function. Human peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) is a multi-functional transcription factor that tightly regulates mitochondrial biogenesis and oxidative capacity. The goal of the present study was to explore the potential pathogenic effects of interference by the PGC-1α gene on N-methyl-4-phenylpyridinium ion (MPP+)-induced SH-SY5Y cells. We utilized RNA interference (RNAi) technology to probe the pathogenic consequences of inhibiting PGC-1α in the SH-SY5Y cell line. Remarkably, a reduction in PGC-1α resulted in the reduction of mitochondrial membrane potential, intracellular ATP content and intracellular H2O2 generation, leading to the translocation of cytochrome c (cyt c) to the cytoplasm in the MPP+-induced PD cell model. The expression of related proteins in the signaling pathway (e.g., estrogen-related receptor α (ERRα), nuclear respiratory factor 1 (NRF-1), NRF-2 and Peroxisome proliferator-activated receptor γ (PPARγ)) also decreased. Our finding indicates that small interfering RNA (siRNA) interference targeting the PGC-1α gene could inhibit the function of mitochondria in several capacities and that the PGC-1α gene may modulate mitochondrial function by regulating the expression of ERRα, NRF-1, NRF-2 and PPARγ. Thus, PGC-1α can be considered a potential therapeutic target for PD. |
| first_indexed | 2024-12-17T13:11:05Z |
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| id | doaj.art-152c4d75206f4cf5bcf076481646f747 |
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| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-17T13:11:05Z |
| publishDate | 2017-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-152c4d75206f4cf5bcf076481646f7472022-12-21T21:47:07ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992017-05-011010.3389/fnmol.2017.00164258910Mitochondrial Effects of PGC-1alpha Silencing in MPP+ Treated Human SH-SY5Y Neuroblastoma CellsQinyong Ye0Qinyong Ye1Chun Chen2Erwang Si3Yousheng Cai4Juhua Wang5Wanling Huang6Dongzhu Li7Yingqing Wang8Xiaochun Chen9Xiaochun Chen10Department of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union HospitalFuzhou, ChinaKey Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical UniversityFuzhou, ChinaDepartment of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union HospitalFuzhou, ChinaDepartment of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union HospitalFuzhou, ChinaDepartment of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union HospitalFuzhou, ChinaDepartment of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union HospitalFuzhou, ChinaDepartment of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union HospitalFuzhou, ChinaDepartment of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union HospitalFuzhou, ChinaDepartment of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union HospitalFuzhou, ChinaDepartment of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union HospitalFuzhou, ChinaKey Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical UniversityFuzhou, ChinaThe dopaminergic neuron degeneration and loss that occurs in Parkinson’s disease (PD) has been tightly linked to mitochondrial dysfunction. Although the aged-related cause of the mitochondrial defect observed in PD patients remains unclear, nuclear genes are of potential importance to mitochondrial function. Human peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) is a multi-functional transcription factor that tightly regulates mitochondrial biogenesis and oxidative capacity. The goal of the present study was to explore the potential pathogenic effects of interference by the PGC-1α gene on N-methyl-4-phenylpyridinium ion (MPP+)-induced SH-SY5Y cells. We utilized RNA interference (RNAi) technology to probe the pathogenic consequences of inhibiting PGC-1α in the SH-SY5Y cell line. Remarkably, a reduction in PGC-1α resulted in the reduction of mitochondrial membrane potential, intracellular ATP content and intracellular H2O2 generation, leading to the translocation of cytochrome c (cyt c) to the cytoplasm in the MPP+-induced PD cell model. The expression of related proteins in the signaling pathway (e.g., estrogen-related receptor α (ERRα), nuclear respiratory factor 1 (NRF-1), NRF-2 and Peroxisome proliferator-activated receptor γ (PPARγ)) also decreased. Our finding indicates that small interfering RNA (siRNA) interference targeting the PGC-1α gene could inhibit the function of mitochondria in several capacities and that the PGC-1α gene may modulate mitochondrial function by regulating the expression of ERRα, NRF-1, NRF-2 and PPARγ. Thus, PGC-1α can be considered a potential therapeutic target for PD.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00164/fullParkinson’s diseaseSH-SY5Y cellsPGC-1αRNA interferenceERRα |
| spellingShingle | Qinyong Ye Qinyong Ye Chun Chen Erwang Si Yousheng Cai Juhua Wang Wanling Huang Dongzhu Li Yingqing Wang Xiaochun Chen Xiaochun Chen Mitochondrial Effects of PGC-1alpha Silencing in MPP+ Treated Human SH-SY5Y Neuroblastoma Cells Frontiers in Molecular Neuroscience Parkinson’s disease SH-SY5Y cells PGC-1α RNA interference ERRα |
| title | Mitochondrial Effects of PGC-1alpha Silencing in MPP+ Treated Human SH-SY5Y Neuroblastoma Cells |
| title_full | Mitochondrial Effects of PGC-1alpha Silencing in MPP+ Treated Human SH-SY5Y Neuroblastoma Cells |
| title_fullStr | Mitochondrial Effects of PGC-1alpha Silencing in MPP+ Treated Human SH-SY5Y Neuroblastoma Cells |
| title_full_unstemmed | Mitochondrial Effects of PGC-1alpha Silencing in MPP+ Treated Human SH-SY5Y Neuroblastoma Cells |
| title_short | Mitochondrial Effects of PGC-1alpha Silencing in MPP+ Treated Human SH-SY5Y Neuroblastoma Cells |
| title_sort | mitochondrial effects of pgc 1alpha silencing in mpp treated human sh sy5y neuroblastoma cells |
| topic | Parkinson’s disease SH-SY5Y cells PGC-1α RNA interference ERRα |
| url | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00164/full |
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