화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.379, No.1, 32-37, 2009
Palmitate alters neuregulin signaling and biology in cardiac myocytes
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-1 beta (NRG-1 beta) is a growth and survival factor in cardiac myocytes. We tested the hypothesis that palmitate alters NRG-1 beta signaling and biology in isolated neonatal rat cardiac myocytes. Palmitate treatment inhibited NRG-1 beta activation of the PI3-kinase/Akt pathway in myocytes. We found that the pro-apoptotic activity of palmitate was increased by NRG-1 beta treatment. The effects of palmitate on NRG-1 beta, signaling and Survival were reversed by the mono-unsaturated fatty acid oleate. Under control conditions NRG-1 beta decreases p53 expression in myocytes. In the presence of palmitate, NRG-1 beta 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-1 beta activates pro-apoptotic, rather than pro-survival signaling in cardiac myocytes. (C) 2008 Elsevier Inc. All rights reserved.