TNF-α signal transduction in rat neonatal cardiac myocytes: Definition of pathways generating from the TNF-α receptor

Gianluigi Condorelli, Carmine Morisco, Michael V G Latronico, Pier Paolo Claudio, Paul Dent, Philip Tsichlis, Gerolama Condorelli, Giacomo Frati, Alessandra Drusco, Carlo M. Croce, Claudio Napoli

Research output: Contribution to journalArticlepeer-review

Abstract

Cardiomyocyte hypertrophy and apoptosis have been implicated in the loss of contractile function during heart failure (HF). Moreover, patients with HF have been shown to exhibit increased levels of tumor necrosis factor α (TNF-α) in the myocardium. However, the multiple signal transduction pathways generating from the TNF-α receptor in cardiomyocytes and leading preferentially to apoptosis or hypertrophy are still unknown. Here we demonstrate in neonatal rat cardiomyocytes that 1) TNF-α induces phosphorylation of AKT, activation of NF-κB, and the phosphorylation of JUN kinase; 2) blocking AKT activity prevents NF-κB activation, suggesting a role for AKT in regulating NF-κB function; 3) AKT and JUN are both critical for the hypertrophic effects of TNF-α, since dominantnegative mutants of these genes are capable of inhibiting TNF-α-induced ANF-promoter up-regulation and increase in cardiomyocyte cell size, and 4) blocking NF-κB, AKT, or JUN alone or in combination does not sensitize cardiomyocytes to the proapoptotic effects of TNF-α, in contrast to other cell types, suggesting a cardiac-specific pathway regulating the anti-apoptotic events induced by TNF-α. Altogether, the data presented evidence the role of AKT and JUN in TNF-αinduced cardiomyocyte hypertrophy and apoptosis. - CondoreUi, G., Morisco, C., Latronico, M., Claudio, P. P., Dent, P., Tsichlis, P., Condorelli, G., Frati, G., Drusco, A., Croce, C. M., Napoli, C. TNF-α signal transduction in rat neonatal cardiac myocytes: definition of pathways generating from the TNF-αreceptor.

Original languageEnglish
Pages (from-to)1732-1737
Number of pages6
JournalFASEB Journal
Volume16
Issue number13
DOIs
Publication statusPublished - Nov 2002

Keywords

  • AKT
  • Cardiomyocyte apoptosis
  • Heart failure
  • Hypertrophy
  • Tumor necrosis factor α

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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