TY - JOUR
T1 - In vitro dexamethasone treatment does not induce alternative ATM transcripts in cells from Ataxia–Telangiectasia patients
AU - Pozzi, Elisa
AU - Giorgio, Elisa
AU - Mancini, Cecilia
AU - Lo Buono, Nicola
AU - Augeri, Stefania
AU - Ferrero, Marta
AU - Di Gregorio, Eleonora
AU - Riberi, Evelise
AU - Vinciguerra, Maria
AU - Nanetti, Lorenzo
AU - Bianchi, Federico Tommaso
AU - Sassi, Maria Paola
AU - Costanzo, Vincenzo
AU - Mariotti, Caterina
AU - Funaro, Ada
AU - Cavalieri, Simona
AU - Brusco, Alfredo
N1 - Funding Information:
The authors are gratefully indebted to the patients and their families for taking part into the study. The work was supported by Associazione “Gli Amici di Valentina”, “Un vero sorriso” and “Noi per Lorenzo”. CM and EG were recipient of a fellowship from Fondazione Umberto Veronesi 2017–2018. This research received funding specifically appointed to Department of Medical Sciences from the Italian Ministry for Education, University and Research (Ministero dell’Istruzione, dell’Università e della Ricerca—MIUR) under the programme “Dipartimenti di Eccellenza 2018–2022” Project code D15D18000410001. We also thank Drs. Stefania Saoncella, Beatrice Tas-sone and Vincenzo Calautti for technical help and critical discussion.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-020-77352-z
DO - 10.1038/s41598-020-77352-z
M3 - Article
C2 - 33214630
AN - SCOPUS:85096337907
VL - 10
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 20182
ER -