RGD Reference Report - Analysis of p53 and NF-kappaB signaling in modulating the cardiomyocyte fate during hypertrophy. - Rat Genome Database

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Analysis of p53 and NF-kappaB signaling in modulating the cardiomyocyte fate during hypertrophy.

Authors: Chatterjee, A  Mir, SA  Dutta, D  Mitra, A  Pathak, K  Sarkar, S 
Citation: Chatterjee A, etal., J Cell Physiol. 2011 Oct;226(10):2543-54. doi: 10.1002/jcp.22599.
RGD ID: 7349387
Pubmed: PMID:21792911   (View Abstract at PubMed)
DOI: DOI:10.1002/jcp.22599   (Journal Full-text)

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, beta-MHC), apoptotic proteins (Bax, Bad, Fas, p53, caspase-3, PARP), and anti-apoptotic or cell proliferation marker proteins (Bcl2, NF-kappaB, 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-kappaBp65 binding to co-activator p300 was also increased in AngII treated myocytes. Inhibition of p53 resulted in downregulation of apoptosis, NF-kappaB activation, and NF-kappaB-p300 binding; however, NF-kappaB inhibition did not inhibit apoptosis or p53-p300 binding. Blocking of either p53 or NF-kappaB 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-kappaB. Thus, these results indicate the crucial role of p53 in regulating both apoptotic and cell proliferation during hypertrophy.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
p53 binding  IPITp53 (Rattus norvegicus)7349387 RGD 
transcription coregulator binding  IPIEp300 (Rattus norvegicus)7349387 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ep300  (E1A binding protein p300)
Tp53  (tumor protein p53)


Additional Information