Scientific reports · 2020
In vitro dexamethasone treatment does not induce alternative ATM transcripts in cells from Ataxia-Telangiectasia patients.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Pozzi Elisa, Giorgio Elisa, Mancini Cecilia, Lo Buono Nicola, Augeri Stefania, Ferrero Marta, Di Gregorio Eleonora, Riberi Evelise, Vinciguerra Maria, Nanetti Lorenzo, Bianchi Federico Tommaso, Sassi Maria Paola, Costanzo Vincenzo, Mariotti Caterina, Funaro Ada, Cavalieri Simona, Brusco Alfredo
Аннотация
Short term treatment with low doses of glucocorticoid analogues has been shown to ameliorate neurological symptoms in Ataxia-Telangiectasia (A-T), a rare autosomal recessive multisystem disease that mainly affects the cerebellum, immune system, and lungs. Molecular mechanisms underlying this clinical observation are unclear. We aimed at evaluating the effect of dexamethasone on the induction of alternative ATM transcripts (ATMdexa1). We showed that dexamethasone cannot induce an alternative ATM transcript in control and A-T lymphoblasts and primary fibroblasts, or in an ATM-knockout HeLa cell line. We also demonstrated that some of the reported readouts associated with ATMdexa1 are due to cellular artifacts and the direct induction of γH2AX by dexamethasone via DNA-PK. Finally, we suggest caution in interpreting dexamethasone effects in vitro for the results to be translated into a rational use of the drug in A-T patients.