HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

NF-κB inhibition compromises cardiac fibroblast viability under hypoxia.

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.
AuthorsM Sangeetha, Malini S Pillai, Linda Philip, Edward G Lakatta, K Shivakumar
JournalExperimental cell research (Exp Cell Res) Vol. 317 Issue 7 Pg. 899-909 (Apr 15 2011) ISSN: 1090-2422 [Electronic] United States
PMID21211536 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier Inc. All rights reserved.
Chemical References
  • BAY 11-7085
  • Inhibitor of Apoptosis Proteins
  • NF-kappa B
  • Nitriles
  • Proto-Oncogene Proteins c-bcl-2
  • Sulfones
  • Caspase 3
Topics
  • Animals
  • Caspase 3 (metabolism)
  • Cell Survival (physiology)
  • Fibroblasts (cytology, drug effects, physiology)
  • Hypoxia (metabolism)
  • Inhibitor of Apoptosis Proteins (genetics, metabolism)
  • Male
  • Myocytes, Cardiac (cytology, drug effects, physiology)
  • NF-kappa B (antagonists & inhibitors)
  • Nitriles (pharmacology)
  • Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Sulfones (pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: