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Author Sangeetha, M. ♦ Pillai, Malini S. ♦ Philip, Linda ♦ Lakatta, E. G. ♦ Shivakumar, K.
Source Sree Chitra Tirunal Institute for Medical Sciences & Technology
Content type Text
Publisher Experimental Cell Research
File Format PDF
Language English
Subject Domain (in DDC) Technology ♦ Medicine & health ♦ Diseases
Subject Domain (in MeSH) Cardiovascular Diseases ♦ Diseases
Subject Keyword Cardiology
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-kappa B protects cardiac fibroblasts from hypoxia-induced cell death. Further, we examined the expression of the antiapoptotic clAP-2 and Bcl-2 in hypoxic cardiac fibroblasts, and their possible regulation by NF-kappa B. 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-kappa B in cardiac fibroblasts. Supershift assay indicated that the active NF-kappa B complex is a p65/p50 heterodimer. An I-kappa B-super-repressor was constructed that prevented NF-kappa B activation and compromised cell viability under hypoxic but not normoxic conditions. Similar results were obtained with Bay 11-7085, an inhibitor of NF-kappa B. Western blot analysis showed constitutive levels of Bcl-2 and hypoxic induction of clAP-2 in these cells. NF-kappa B inhibition reduced clAP-2 but not Bcl-2 levels in hypoxic cardiac fibroblasts. The results show for the first time that NF-kappa B is an important effector of survival in cardiac fibroblasts under hypoxic stress and that regulation of clAP-2 expression may contribute to its pro-survival role. (C) 2011 Elsevier Inc. All rights reserved.
Education Level UG and PG
Learning Resource Type Article
Educational Framework Medical Council of India (MCI)
Volume Number 317
Issue Number 7
Page Count 11
Starting Page 899
Ending Page 909