NF-κB inhibition compromises cardiac fibroblast viability under hypoxia.
Exp Cell Res
; 317(7): 899-909, 2011 Apr 15.
Article
en En
| MEDLINE
| ID: mdl-21211536
ABSTRACT
Cardiac fibroblasts are reported to be relatively resistant to stress stimuli compared to cardiac myocytes and fibroblasts of non-cardiac origin. However, the mechanisms that facilitate their survival under conditions of stress remain unclear. We explored the possibility that NF-κB protects cardiac fibroblasts from hypoxia-induced cell death. Further, we examined the expression of the antiapoptotic cIAP-2 and Bcl-2 in hypoxic cardiac fibroblasts, and their possible regulation by NF-κB. Phase contrast microscopy and propidium iodide staining revealed that cardiac fibroblasts are more resistant than pulmonary fibroblasts to hypoxia. Electrophoretic Mobility Shift Assay showed that hypoxia activates NF-κB in cardiac fibroblasts. Supershift assay indicated that the active NF-κB complex is a p65/p50 heterodimer. An I-κB-super-repressor was constructed that prevented NF-κB activation and compromised cell viability under hypoxic but not normoxic conditions. Similar results were obtained with Bay 11-7085, an inhibitor of NF-κB. Western blot analysis showed constitutive levels of Bcl-2 and hypoxic induction of cIAP-2 in these cells. NF-κB inhibition reduced cIAP-2 but not Bcl-2 levels in hypoxic cardiac fibroblasts. The results show for the first time that NF-κB is an important effector of survival in cardiac fibroblasts under hypoxic stress and that regulation of cIAP-2 expression may contribute to its pro-survival role.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Supervivencia Celular
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FN-kappa B
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Miocitos Cardíacos
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Fibroblastos
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Hipoxia
Límite:
Animals
Idioma:
En
Revista:
Exp Cell Res
Año:
2011
Tipo del documento:
Article
País de afiliación:
India