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 language||English (US)|
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Jan 30 2009|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology