title: Analysis of p53 and NF-κB signaling in modulating the cardiomyocyte fate during hypertrophy.
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.
authors.affiliation: Department of Zoology, University of Calcutta, Kolkata, West Bengal, India.
authors.forename: Arunachal
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Saiful A
authors.initials: SA
authors.lastname: Mir
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Dutta
authors.forename: Arkadeep
authors.initials: A
authors.lastname: Mitra
authors.forename: Kanchan
authors.initials: K
authors.lastname: Pathak
authors.forename: Sagartirtha
authors.initials: S
authors.lastname: Sarkar
mesh_terms: D000367:Age Factors; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D014662:Vasoconstrictor Agents; D000804:Angiotensin II