Natural Antioxidants Reduce Oxidative Stress and the Toxic Effects of RNA-CUG<sub>(exp)</sub> in an Inducible Glial Myotonic Dystrophy Type 1 Cell Model
The toxic gain-of-function of RNA-CUG<sub>(exp)</sub> in DM1 has been largely studied in skeletal muscle, with little focus on its effects on the central nervous system (CNS). This study aimed to study if oxidative stress is present in DM1, its relationship with the toxic RNA gain-of-fun...
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2025-02-01
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| author | Fernando Morales Dayana Vargas Melissa Palma-Jiménez Esteban J. Rodríguez Gabriela Azofeifa Oscar Hernández-Hernández |
| author_facet | Fernando Morales Dayana Vargas Melissa Palma-Jiménez Esteban J. Rodríguez Gabriela Azofeifa Oscar Hernández-Hernández |
| author_sort | Fernando Morales |
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| description | The toxic gain-of-function of RNA-CUG<sub>(exp)</sub> in DM1 has been largely studied in skeletal muscle, with little focus on its effects on the central nervous system (CNS). This study aimed to study if oxidative stress is present in DM1, its relationship with the toxic RNA gain-of-function and if natural antioxidants can revert some of the RNA-CUG<sub>(exp)</sub> toxic effects. Using an inducible glial DM1 model (MIO-M1 cells), we compared OS in expanded vs. unexpanded cells and investigated whether antioxidants can mitigate OS and RNA-CUG<sub>(exp)</sub> toxicity. OS was measured via superoxide anion and lipid peroxidation assays. RNA foci were identified using FISH, and the mis-splicing of selected exons was analyzed using semi-quantitative RT-PCR. Cells were treated with natural antioxidants, and the effects on OS, foci formation, and mis-splicing were compared between treated and untreated cells. The results showed significantly higher superoxide anion and lipid peroxidation levels in untreated DM1 cells, which decreased after antioxidant treatment (ANOVA, <i>p</i> < 0.001). Foci were present in 51% of the untreated cells but were reduced in a dose-dependent manner following treatment (ANOVA, <i>p</i> < 0.001). Antioxidants also improved the splicing of selected exons (ANOVA, <i>p</i> < 0.001), suggesting OS plays a role in DM1, and antioxidants may offer therapeutic potential. |
| format | Article |
| id | doaj-art-7a60e3b968de4c95a1a55c84dad44351 |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-02-01 |
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| series | Antioxidants |
| spelling | doaj-art-7a60e3b968de4c95a1a55c84dad443512025-08-20T03:40:43ZengMDPI AGAntioxidants2076-39212025-02-0114326010.3390/antiox14030260Natural Antioxidants Reduce Oxidative Stress and the Toxic Effects of RNA-CUG<sub>(exp)</sub> in an Inducible Glial Myotonic Dystrophy Type 1 Cell ModelFernando Morales0Dayana Vargas1Melissa Palma-Jiménez2Esteban J. Rodríguez3Gabriela Azofeifa4Oscar Hernández-Hernández5Instituto de Investigaciones en Salud (INISA), Universidad de Costa Rica, San José 2060, Costa RicaInstituto de Investigaciones en Salud (INISA), Universidad de Costa Rica, San José 2060, Costa RicaInstituto de Investigaciones en Salud (INISA), Universidad de Costa Rica, San José 2060, Costa RicaInstituto de Investigaciones en Salud (INISA), Universidad de Costa Rica, San José 2060, Costa RicaDepartamento de Bioquímica, Escuela de Medicina, Universidad de Costa Rica, San José 2060, Costa RicaLaboratorio de Medicina Genómica, Departamento de Genética, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, INR-LGII, Mexico City 14389, MexicoThe toxic gain-of-function of RNA-CUG<sub>(exp)</sub> in DM1 has been largely studied in skeletal muscle, with little focus on its effects on the central nervous system (CNS). This study aimed to study if oxidative stress is present in DM1, its relationship with the toxic RNA gain-of-function and if natural antioxidants can revert some of the RNA-CUG<sub>(exp)</sub> toxic effects. Using an inducible glial DM1 model (MIO-M1 cells), we compared OS in expanded vs. unexpanded cells and investigated whether antioxidants can mitigate OS and RNA-CUG<sub>(exp)</sub> toxicity. OS was measured via superoxide anion and lipid peroxidation assays. RNA foci were identified using FISH, and the mis-splicing of selected exons was analyzed using semi-quantitative RT-PCR. Cells were treated with natural antioxidants, and the effects on OS, foci formation, and mis-splicing were compared between treated and untreated cells. The results showed significantly higher superoxide anion and lipid peroxidation levels in untreated DM1 cells, which decreased after antioxidant treatment (ANOVA, <i>p</i> < 0.001). Foci were present in 51% of the untreated cells but were reduced in a dose-dependent manner following treatment (ANOVA, <i>p</i> < 0.001). Antioxidants also improved the splicing of selected exons (ANOVA, <i>p</i> < 0.001), suggesting OS plays a role in DM1, and antioxidants may offer therapeutic potential.https://www.mdpi.com/2076-3921/14/3/260myotonic dystrophyRNA toxic gain-of-functioninducible modelglial cell modelantioxidantstreatment |
| spellingShingle | Fernando Morales Dayana Vargas Melissa Palma-Jiménez Esteban J. Rodríguez Gabriela Azofeifa Oscar Hernández-Hernández Natural Antioxidants Reduce Oxidative Stress and the Toxic Effects of RNA-CUG<sub>(exp)</sub> in an Inducible Glial Myotonic Dystrophy Type 1 Cell Model Antioxidants myotonic dystrophy RNA toxic gain-of-function inducible model glial cell model antioxidants treatment |
| title | Natural Antioxidants Reduce Oxidative Stress and the Toxic Effects of RNA-CUG<sub>(exp)</sub> in an Inducible Glial Myotonic Dystrophy Type 1 Cell Model |
| title_full | Natural Antioxidants Reduce Oxidative Stress and the Toxic Effects of RNA-CUG<sub>(exp)</sub> in an Inducible Glial Myotonic Dystrophy Type 1 Cell Model |
| title_fullStr | Natural Antioxidants Reduce Oxidative Stress and the Toxic Effects of RNA-CUG<sub>(exp)</sub> in an Inducible Glial Myotonic Dystrophy Type 1 Cell Model |
| title_full_unstemmed | Natural Antioxidants Reduce Oxidative Stress and the Toxic Effects of RNA-CUG<sub>(exp)</sub> in an Inducible Glial Myotonic Dystrophy Type 1 Cell Model |
| title_short | Natural Antioxidants Reduce Oxidative Stress and the Toxic Effects of RNA-CUG<sub>(exp)</sub> in an Inducible Glial Myotonic Dystrophy Type 1 Cell Model |
| title_sort | natural antioxidants reduce oxidative stress and the toxic effects of rna cug sub exp sub in an inducible glial myotonic dystrophy type 1 cell model |
| topic | myotonic dystrophy RNA toxic gain-of-function inducible model glial cell model antioxidants treatment |
| url | https://www.mdpi.com/2076-3921/14/3/260 |
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