In vitro dexamethasone treatment does not induce alternative ATM transcripts in cells from Ataxia–Telangiectasia patients

Elisa Pozzi, Elisa Giorgio, Cecilia Mancini, Nicola Lo Buono, Stefania Augeri, Marta Ferrero, Eleonora Di Gregorio, Evelise Riberi, Maria Vinciguerra, Lorenzo Nanetti, Federico Tommaso Bianchi, Maria Paola Sassi, Vincenzo Costanzo, Caterina Mariotti, Ada Funaro, Simona Cavalieri, Alfredo Brusco

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Abstract

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.

Original languageEnglish
Article number20182
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 2020

ASJC Scopus subject areas

  • General

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