Uridine Prevents Negative Effects of OXPHOS Xenobiotics on Dopaminergic Neuronal Differentiation
Neuronal differentiation appears to be dependent on oxidative phosphorylation capacity. Several drugs inhibit oxidative phosphorylation and might be detrimental for neuronal differentiation. Some pregnant women take these medications during their first weeks of gestation when fetal nervous system is...
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MDPI AG
2019-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/11/1407 |
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| author | Eldris Iglesias M. Pilar Bayona-Bafaluy Alba Pesini Nuria Garrido-Pérez Patricia Meade Paula Gaudó Irene Jiménez-Salvador Julio Montoya Eduardo Ruiz-Pesini |
| author_facet | Eldris Iglesias M. Pilar Bayona-Bafaluy Alba Pesini Nuria Garrido-Pérez Patricia Meade Paula Gaudó Irene Jiménez-Salvador Julio Montoya Eduardo Ruiz-Pesini |
| author_sort | Eldris Iglesias |
| collection | DOAJ |
| description | Neuronal differentiation appears to be dependent on oxidative phosphorylation capacity. Several drugs inhibit oxidative phosphorylation and might be detrimental for neuronal differentiation. Some pregnant women take these medications during their first weeks of gestation when fetal nervous system is being developed. These treatments might have later negative consequences on the offspring’s health. To analyze a potential negative effect of three widely used medications, we studied in vitro dopaminergic neuronal differentiation of cells exposed to pharmacologic concentrations of azidothymidine for acquired immune deficiency syndrome; linezolid for multidrug-resistant tuberculosis; and atovaquone for malaria. We also analyzed the dopaminergic neuronal differentiation in brains of fetuses from pregnant mice exposed to linezolid. The drugs reduced the in vitro oxidative phosphorylation capacity and dopaminergic neuronal differentiation. This differentiation process does not appear to be affected in the prenatally exposed fetus brain. Nevertheless, the global DNA methylation in fetal brain was significantly altered, perhaps linking an early exposure to a negative effect in older life. Uridine was able to prevent the negative effects on in vitro dopaminergic neuronal differentiation and on in vivo global DNA methylation. Uridine could be used as a protective agent against oxidative phosphorylation-inhibiting pharmaceuticals provided during pregnancy when dopaminergic neuronal differentiation is taking place. |
| first_indexed | 2024-03-12T07:19:19Z |
| format | Article |
| id | doaj.art-8eab835bfdb349b4b73e4cd0e4b9c267 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:19:19Z |
| publishDate | 2019-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-8eab835bfdb349b4b73e4cd0e4b9c2672023-09-02T22:33:22ZengMDPI AGCells2073-44092019-11-01811140710.3390/cells8111407cells8111407Uridine Prevents Negative Effects of OXPHOS Xenobiotics on Dopaminergic Neuronal DifferentiationEldris Iglesias0M. Pilar Bayona-Bafaluy1Alba Pesini2Nuria Garrido-Pérez3Patricia Meade4Paula Gaudó5Irene Jiménez-Salvador6Julio Montoya7Eduardo Ruiz-Pesini8Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, SpainDepartamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, SpainDepartamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, SpainDepartamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, SpainDepartamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, SpainDepartamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, SpainDepartamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, SpainDepartamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, SpainDepartamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, SpainNeuronal differentiation appears to be dependent on oxidative phosphorylation capacity. Several drugs inhibit oxidative phosphorylation and might be detrimental for neuronal differentiation. Some pregnant women take these medications during their first weeks of gestation when fetal nervous system is being developed. These treatments might have later negative consequences on the offspring’s health. To analyze a potential negative effect of three widely used medications, we studied in vitro dopaminergic neuronal differentiation of cells exposed to pharmacologic concentrations of azidothymidine for acquired immune deficiency syndrome; linezolid for multidrug-resistant tuberculosis; and atovaquone for malaria. We also analyzed the dopaminergic neuronal differentiation in brains of fetuses from pregnant mice exposed to linezolid. The drugs reduced the in vitro oxidative phosphorylation capacity and dopaminergic neuronal differentiation. This differentiation process does not appear to be affected in the prenatally exposed fetus brain. Nevertheless, the global DNA methylation in fetal brain was significantly altered, perhaps linking an early exposure to a negative effect in older life. Uridine was able to prevent the negative effects on in vitro dopaminergic neuronal differentiation and on in vivo global DNA methylation. Uridine could be used as a protective agent against oxidative phosphorylation-inhibiting pharmaceuticals provided during pregnancy when dopaminergic neuronal differentiation is taking place.https://www.mdpi.com/2073-4409/8/11/1407oxidative phosphorylationxenobioticslinezoliduridineneuronal differentiationparkinson’s disease |
| spellingShingle | Eldris Iglesias M. Pilar Bayona-Bafaluy Alba Pesini Nuria Garrido-Pérez Patricia Meade Paula Gaudó Irene Jiménez-Salvador Julio Montoya Eduardo Ruiz-Pesini Uridine Prevents Negative Effects of OXPHOS Xenobiotics on Dopaminergic Neuronal Differentiation Cells oxidative phosphorylation xenobiotics linezolid uridine neuronal differentiation parkinson’s disease |
| title | Uridine Prevents Negative Effects of OXPHOS Xenobiotics on Dopaminergic Neuronal Differentiation |
| title_full | Uridine Prevents Negative Effects of OXPHOS Xenobiotics on Dopaminergic Neuronal Differentiation |
| title_fullStr | Uridine Prevents Negative Effects of OXPHOS Xenobiotics on Dopaminergic Neuronal Differentiation |
| title_full_unstemmed | Uridine Prevents Negative Effects of OXPHOS Xenobiotics on Dopaminergic Neuronal Differentiation |
| title_short | Uridine Prevents Negative Effects of OXPHOS Xenobiotics on Dopaminergic Neuronal Differentiation |
| title_sort | uridine prevents negative effects of oxphos xenobiotics on dopaminergic neuronal differentiation |
| topic | oxidative phosphorylation xenobiotics linezolid uridine neuronal differentiation parkinson’s disease |
| url | https://www.mdpi.com/2073-4409/8/11/1407 |
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