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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)
Journal EXPERIMENTAL CELL RESEARCH
Volume Number 317
Issue Number 7
Page Count 11
Starting Page 899
Ending Page 909