Document Detail

Nuclear lipid microdomains regulate nuclear vitamin D3 uptake and influence embryonic hippocampal cell differentiation.
MedLine Citation:
PMID:  21737687     Owner:  NLM     Status:  MEDLINE    
Despite recent advances in the understanding of the role of 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) in the CNS, the mechanism of action remains obscure. We demonstrate that some 1,25-(OH)(2)D(3) receptor (VDR) is localized in the cell nucleus in specialized microdomains enriched in sphingomyelin and cholesterol; the integrity of these microdomains is necessary for embryonic hippocampal cell differentiation. Sphingomyelinase (SMase) treatment reduces both VDR and labeled 1,25-(OH)(2)D(3) content in nuclear microdomains. We have previously shown that HN9.10e embryonic hippocampal cells differentiate when incubated with 100 nM 1,25-(OH)(2)D(3) in the presence of 10% fetal calf serum, while serum deprivation induces cell death. In this study, we have investigated whether conditions that alter lipid content of nuclear microdomains modify 1,25-(OH)(2)D(3)-induced differentiation. Serum deprivation activates SMase and modifies the composition of nuclear microdomains, which lose the 1,25-(OH)(2) vitamin D(3) receptor. The incubation of serum-deprived cells with 100 nM 1,25-(OH)(2)D(3) prevents differentiation. However, treatment with 400 nM 1,25-(OH)(2)D(3) during serum withdrawal increases the lipid content of the nuclear microdomains, allows the interaction of 1,25-(OH)(2)D(3) with its receptor, and results in differentiation. These results suggest the presence of VDR in nuclear microdomains is necessary for 1,25-(OH)(2)D(3)-induced differentiation in embryonic hippocampal cells.
Elisa Bartoccini; Francesca Marini; Eleni Damaskopoulou; Remo Lazzarini; Samuela Cataldi; Giacomo Cascianelli; Mercedes Gil Garcia; Elisabetta Albi
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Publication Detail:
Type:  Journal Article     Date:  2011-07-07
Journal Detail:
Title:  Molecular biology of the cell     Volume:  22     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-08-31     Completed Date:  2011-12-30     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3022-31     Citation Subset:  IM    
Physiopathology Section, Department of Clinical and Experimental Medicine, University School of Medicine, University of Perugia, Perugia, Italy.
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MeSH Terms
Cell Differentiation*
Cell Line
Cell Nucleus / metabolism*
Cell Shape
Cholecalciferol / pharmacology*,  physiology
Hippocampus / cytology,  embryology*,  metabolism
Lipid Metabolism
Membrane Microdomains / metabolism*
Nerve Growth Factor / metabolism
Nuclear Envelope / metabolism*
Proto-Oncogene Proteins / metabolism
Receptors, Calcitriol / metabolism
Sphingomyelin Phosphodiesterase / pharmacology,  physiology
Sphingomyelins / metabolism
Reg. No./Substance:
0/Proto-Oncogene Proteins; 0/Receptors, Calcitriol; 0/Sphingomyelins; 114100-40-2/Bcl2 protein, mouse; 67-97-0/Cholecalciferol; 9061-61-4/Nerve Growth Factor; EC Phosphodiesterase

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