Palmitate alters neuregulin signaling and biology in cardiac myocytes

Thomas A. Miller, Basak Icli, Gregory M. Cote, Nathan K. LeBrasseur, Steve C. Borkan, David R. Pimentel, Xuyang Peng, Douglas B. Sawyer

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The saturated fatty acid palmitate alters normal cell function via disruption of cell signaling, and this effect has been implicated in the end-organ damage associated with dyslipidemia. Neuregulin-1β (NRG-1β) is a growth and survival factor in cardiac myocytes. We tested the hypothesis that palmitate alters NRG-1β signaling and biology in isolated neonatal rat cardiac myocytes. Palmitate treatment inhibited NRG-1β activation of the PI3-kinase/Akt pathway in myocytes. We found that the pro-apoptotic activity of palmitate was increased by NRG-1β treatment. The effects of palmitate on NRG-1β signaling and survival were reversed by the mono-unsaturated fatty acid oleate. Under control conditions NRG-1β decreases p53 expression in myocytes. In the presence of palmitate, NRG-1β caused an increase in p53 expression, bax multimer formation, concurrent with degradation of mdm2, a negative regulator of p53. Thus in the presence of palmitate NRG-1β activates pro-apoptotic, rather than pro-survival signaling in cardiac myocytes.

Original languageEnglish (US)
Pages (from-to)32-37
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume379
Issue number1
DOIs
StatePublished - Jan 30 2009

Keywords

  • Apoptosis
  • Heart
  • Heregulin
  • Lipotoxicity
  • Neuregulin
  • Palmitate
  • erbB2
  • erbB4

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Miller, T. A., Icli, B., Cote, G. M., LeBrasseur, N. K., Borkan, S. C., Pimentel, D. R., Peng, X., & Sawyer, D. B. (2009). Palmitate alters neuregulin signaling and biology in cardiac myocytes. Biochemical and Biophysical Research Communications, 379(1), 32-37. https://doi.org/10.1016/j.bbrc.2008.11.150