Deleted in Breast Cancer 1 regulates cellular senescence during obesity.
Aging Cell
; 13(5): 951-3, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-24992635
ABSTRACT
Chronic obesity leads to inflammation, tissue dysfunction, and cellular senescence. It was proposed that cellular senescence during obesity and aging drives inflammation and dysfunction. Consistent with this, clearance of senescent cells increases healthspan in progeroid mice. Here, we show that the protein Deleted in Breast Cancer-1 (DBC1) regulates cellular senescence during obesity. Deletion of DBC1 protects preadipocytes against cellular senescence and senescence-driven inflammation. Furthermore, we show protection against cellular senescence in DBC1 KO mice during obesity. Finally, we found that DBC1 participates in the onset of cellular senescence in response to cell damage by mechanism that involves binding and inhibition of HDAC3. We propose that by regulating HDAC3 activity during cellular damage, DBC1 participates in the fate decision that leads to the establishment of cellular senescence and consequently to inflammation and tissue dysfunction during obesity.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Senescência Celular
/
Proteínas Adaptadoras de Transdução de Sinal
/
Inflamação
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Obesidade
Limite:
Animals
Idioma:
En
Revista:
Aging Cell
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Uruguai