Nitric oxide modulates chromatin folding in human endothelial cells via protein phosphatase 2A activation and class II histone deacetylases nuclear shuttling.
Circ Res
; 102(1): 51-8, 2008 Jan 04.
Article
em En
| MEDLINE
| ID: mdl-17975112
ABSTRACT
Nitric oxide (NO) modulates important endothelial cell (EC) functions and gene expression by a molecular mechanism which is still poorly characterized. Here we show that in human umbilical vein ECs (HUVECs) NO inhibited serum-induced histone acetylation and enhanced histone deacetylase (HDAC) activity. By immunofluorescence and Western blot analyses it was found that NO induced class II HDAC4 and 5 nuclear shuttling and that class II HDACs selective inhibitor MC1568 rescued serum-dependent histone acetylation above control level in NO-treated HUVECs. In contrast, class I HDACs inhibitor MS27-275 had no effect, indicating a specific role for class II HDACs in NO-dependent histone deacetylation. In addition, it was found that NO ability to induce HDAC4 and HDAC5 nuclear shuttling involved the activation of the protein phosphatase 2A (PP2A). In fact, HDAC4 nuclear translocation was impaired in ECs expressing small-t antigen and exposed to NO. Finally, in cells engineered to express a HDAC4-Flag fusion protein, NO induced the formation of a macromolecular complex including HDAC4, HDAC3, HDAC5, and an active PP2A. The present results show that NO-dependent PP2A activation plays a key role in class II HDACs nuclear translocation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirróis
/
Endotélio Vascular
/
Transporte Ativo do Núcleo Celular
/
Células Endoteliais
/
Montagem e Desmontagem da Cromatina
/
Proteína Fosfatase 2
/
Histona Desacetilases
/
Ácidos Hidroxâmicos
/
Óxido Nítrico
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Circ Res
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Itália