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

11 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Neuregulins
Neuregulin-1
Palmitates
Cardiac Myocytes
Muscle Cells
Monounsaturated fatty acids
Cell signaling
Oleic Acid
Dyslipidemias
Unsaturated Fatty Acids
Phosphatidylinositol 3-Kinases
Rats
Intercellular Signaling Peptides and Proteins
Fatty Acids
Chemical activation
Degradation

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Palmitate alters neuregulin signaling and biology in cardiac myocytes. / Miller, Thomas A.; Icli, Basak; Cote, Gregory M.; LeBrasseur, Nathan K; Borkan, Steve C.; Pimentel, David R.; Peng, Xuyang; Sawyer, Douglas B.

In: Biochemical and Biophysical Research Communications, Vol. 379, No. 1, 30.01.2009, p. 32-37.

Research output: Contribution to journalArticle

Miller, Thomas A. ; Icli, Basak ; Cote, Gregory M. ; LeBrasseur, Nathan K ; Borkan, Steve C. ; Pimentel, David R. ; Peng, Xuyang ; Sawyer, Douglas B. / Palmitate alters neuregulin signaling and biology in cardiac myocytes. In: Biochemical and Biophysical Research Communications. 2009 ; Vol. 379, No. 1. pp. 32-37.
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