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Analysis of p53 and NF‐κB signaling in modulating the cardiomyocyte fate during hypertrophy
Author(s) -
Chatterjee Arunachal,
Mir Saiful A.,
Dutta Dipanjan,
Mitra Arkadeep,
Pathak Kanchan,
Sarkar Sagartirtha
Publication year - 2011
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22599
Subject(s) - apoptosis , muscle hypertrophy , angiotensin ii , myocyte , downregulation and upregulation , cell growth , biology , microbiology and biotechnology , nf κb , medicine , cancer research , endocrinology , cell , signal transduction , biochemistry , gene , blood pressure
Abstract Cardiac hypertrophy leading to eventual heart failure is the most common cause of mortality throughout the world. The triggering mechanisms for cardiac hypertrophy are not clear but both apoptosis and cell proliferation have been reported in sections of failing hearts. In this study, we utilized both angiotensin II (AngII) treatment of cardiomyocytes and aortic ligation in rats ( Rattus norvegicus , Wistar strain) for induction of hypertrophy to understand the cellular factors responsible for activation of apoptotic or anti‐apoptotic pathway. Hypertrophy markers ( ANF , β‐MHC ), apoptotic proteins (Bax, Bad, Fas, p53, caspase‐3, PARP), and anti‐apoptotic or cell proliferation marker proteins (Bcl2, NF‐κB, Ki‐67) were induced significantly during hypertrophy, both in vitro as well as in vivo. Co‐localization of both active caspase‐3 and Ki‐67 was observed in hypertrophied myocytes. p53 and NF‐κBp65 binding to co‐activator p300 was also increased in AngII treated myocytes. Inhibition of p53 resulted in downregulation of apoptosis, NF‐κB activation, and NF‐κB–p300 binding; however, NF‐κB inhibition did not inhibit apoptosis or p53–p300 binding. Blocking of either p53 or NF‐κB by specific inhibitors resulted in decrease in cell proliferation and hypertrophy markers, suggesting that p53 initially binds to p300 and then this complex recruits NF‐κB. Thus, these results indicate the crucial role of p53 in regulating both apoptotic and cell proliferation during hypertrophy. J. Cell. Physiol. 226: 2543–2554, 2011. © 2010 Wiley‐Liss, Inc.