Antioxidant treatment ameliorates phenotypic features of SMC1A-mutated Cornelia de Lange syndrome in vitro and in vivo
| Autor: | Bryony Leeke, Dubravka Cukrov, Megan Leask, Julia A. Horsfield, Antonio Musio, Trent Newman, Ian D. Krantz, Antonie D. Kline, Patrizia Sarogni, Alessandra Patimo |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Premature aging Cornelia de Lange Syndrome Chromosomal Proteins Non-Histone Cell Cycle Proteins SMC1A Biology In Vitro Techniques Antioxidants Genomic Instability 03 medical and health sciences De Lange Syndrome Gene expression Genetics medicine Animals Humans Molecular Biology Genetics (clinical) Zebrafish Zinc finger Gene Expression Profiling General Medicine medicine.disease Ascorbic acid Phenotype Molecular biology Gene expression profiling Oxidative Stress 030104 developmental biology Gene Expression Regulation Mutation Biomarkers |
| Zdroj: | Human molecular genetics. 27(17) |
| ISSN: | 1460-2083 |
| Popis: | Cornelia de Lange syndrome (CdLS) is a rare disease characterized by cognitive impairment, multisystemic alterations and premature aging. Furthermore, CdLS cells display gene expression dysregulation and genomic instability. Here, we demonstrated that treatment with antioxidant drugs, such as ascorbic acid and riboceine, reduced the level of genomic instability and extended the in vitro lifespan of CdLS cell lines. We also found that antioxidant treatment partially rescued the phenotype of a zebrafish model of CdLS. Gene expression profiling showed that antioxidant drugs caused dysregulation of gene transcription; notably, a number of genes coding for the zinc finger (ZNF)-containing Krueppel-associated box (KRAB) protein domain (KRAB-ZNF) were found to be downregulated. Taken together, these data suggest that antioxidant drugs have the potential to ameliorate the developmental phenotype of CdLS. |
| Databáze: | OpenAIRE |
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