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

International Journal of Molecular Sciences

Mercedes Garcia-Gil¹  Francesco Saverio Ambesi-Impiombato²  Francesco Curcio²  Michela Codini³  Tommaso Beccari³  Anna Rita Tringali⁴  Sabina Tringali⁴  Samuela Cataldi⁵  Alessandro Floridi⁵  Elisabetta Albi⁵  Elisa Bartoccini⁵  Andrea Lazzarini⁵  Giacomo Cascianelli⁵  Remo Lazzarini⁵ 

[1] Department of Biology, University of Pisa, 56127 Pisa, Italy;Department of Clinical and Biological Sciences, University of Udine, 33100 Udine, Italy;Department of Pharmaceutical Science, University of Perugia, 06100 Perugia, Italy;Laboratory of Clinical Pathology, 96011 Augusta-Siracusa, Italy;Laboratory of Nuclear Lipid BioPathology, Crabion, 06074 Perugia, Italy;

关键词: dexametasone;    lymphoma;    nuclear lipid microdomains;    sphingomyelin;    sphingomyelinase;    sphingomyelin-synthase;   

DOI  :  10.3390/ijms151119832

来源: DOAJ

【 摘 要 】

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 levelis 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 glyceraldehyde3-phosphate dehydrogenase (GAPDH) genes and by the reduction of signal transducerand activator of transcription 3 (STAT3) and phospho signal transducer and activatorof 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.

【 授权许可】

Unknown