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Int. J. Mol. Sci. 2014, 15(11), 19832-19846; doi:10.3390/ijms151119832

Nuclear Lipid Microdomain as Resting Place of Dexamethasone to Impair Cell Proliferation

1
Laboratory of Nuclear Lipid BioPathology, Crabion, 06074 Perugia, Italy
2
Department of Pharmaceutical Science, University of Perugia, 06100 Perugia, Italy
3
Laboratory of Clinical Pathology, 96011 Augusta-Siracusa, Italy
4
Department of Biology, University of Pisa, 56127 Pisa, Italy
5
Department of Clinical and Biological Sciences, University of Udine, 33100 Udine, Italy
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 13 September 2014 / Revised: 24 October 2014 / Accepted: 27 October 2014 / Published: 31 October 2014
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
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Abstract

The action of dexamethasone is initiated by, and strictly dependent upon, the interaction of the drug with its receptor followed by its translocation into the nucleus where modulates gene expression. Where the drug localizes at the intranuclear level is not yet known. We aimed to study the localization of the drug in nuclear lipid microdomains rich in sphingomyelin content that anchor active chromatin and act as platform for transcription modulation. The study was performed in non-Hodgkin’s T cell human lymphoblastic lymphoma (SUP-T1 cell line). We found that when dexamethasone enters into the nucleus it localizes in nuclear lipid microdomains where influences sphingomyelin metabolism. This is followed after 24 h by a cell cycle block accompanied by the up-regulation of cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin-dependent kinase inhibitor 1B (CDKN1B), growth arrest and DNA-damage 45A (GADD45A), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) genes and by the reduction of signal transducer and activator of transcription 3 (STAT3) and phospho signal transducer and activator of transcription 3 (phoshoSTAT3) proteins. After 48 h some cells show morphological changes characteristic of apoptosis while the number of the cells that undergo cell division and express B-cell lymphoma-2 (Bcl-2) is very low. We suggest that the integrity of nuclear lipid microdomains is important for the response to glucocorticoids of cancer cells. View Full-Text
Keywords: dexametasone; lymphoma; nuclear lipid microdomains; sphingomyelin; sphingomyelinase; sphingomyelin-synthase dexametasone; lymphoma; nuclear lipid microdomains; sphingomyelin; sphingomyelinase; sphingomyelin-synthase
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Cataldi, S.; Codini, M.; Cascianelli, G.; Tringali, S.; Tringali, A.R.; Lazzarini, A.; Floridi, A.; Bartoccini, E.; Garcia-Gil, M.; Lazzarini, R.; Ambesi-Impiombato, F.S.; Curcio, F.; Beccari, T.; Albi, E. Nuclear Lipid Microdomain as Resting Place of Dexamethasone to Impair Cell Proliferation. Int. J. Mol. Sci. 2014, 15, 19832-19846.

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