Selective impairment of nuclear factor-κB-dependent gene transcription in adult cardiomyocytes: Relevance for the regulation of the inflammatory response in the heart

Jimena Cuenca, Nora Goren, Patricia Prieto, Paloma Martín-Sanz, Lisardo Boscá*

*Autor correspondiente de este trabajo

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

9 Citas (Scopus)

Resumen

The ability of neonatal and adult cardiomyocytes to activate the nuclear factor (NF)-κB pathway in response to lipopolysaccharide and interleukin-1β challenge has been investigated and compared with that of peritoneal macrophages. The activation of the IκB kinase and the phosphorylation and degradation of IκBα and IκBβ was much lower in adult cardiomyocytes than in the neonatal counterparts and macrophages. This restricted activation of the NF-κB pathway resulted in a significant reduction in the time of nuclear activation of NF-κB, as deduced by electrophoretic mobility shift assays and in the transcription of target genes, such as IκBα, cyclooxygenase-2 (COX-2) and nitric-oxide synthase-2 (NOS-2). Studies on chromatin immunoprecipitation showed binding of NF-κB proteins to the regulatory κB sites identified in the promoters of the IκBα, COX-2, and NOS-2 genes in macrophages and, to a lower extent, in neonatal cardiomyocytes. The binding to these κB sites in adult cardiomyocytes was observed only in the IκBα promoter and was minimal or absent in the COX-2 and NOS-2 promoters, respectively, suggesting a restricted activation of NF-κB-regulated genes in these cells. These data indicate that the function of the NF-κB pathway in adult cardiomyocytes is limited in time, which results in the expression of a reduced number of genes and provides a functional explanation for the absence of NOS-2 inducibility in these cells under proinflammatory conditions.
Idioma originalInglés
Páginas (desde-hasta)820-828
Número de páginas9
PublicaciónAmerican Journal of Pathology
Volumen171
N.º3
DOI
EstadoPublicada - sept. 2007
Publicado de forma externa

Palabras clave

  • animal cell
  • article
  • chromatin immunoprecipitation
  • controlled study
  • enzyme activation
  • gel mobility shift assay
  • gene expression
  • gene targeting
  • genetic transcription
  • heart muscle cell
  • male
  • mouse
  • myocarditis
  • newborn
  • nonhuman
  • peritoneum macrophage
  • priority journal
  • promoter region
  • protein binding
  • protein degradation
  • protein phosphorylation

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