棕榈酸盐会改变心肌细胞中的神经调节蛋白信号传导及生物学特性。
Palmitate alters neuregulin signaling and biology in cardiac myocytes.
作者信息
Miller Thomas A, Icli Basak, Cote Gregory M, Lebrasseur Nathan K, Borkan Steve C, Pimentel David R, Peng Xuyang, Sawyer Douglas B
机构信息
Boston University School of Medicine, Department of Medicine, Boston, MA, USA.
出版信息
Biochem Biophys Res Commun. 2009 Jan 30;379(1):32-7. doi: 10.1016/j.bbrc.2008.11.150. Epub 2008 Dec 12.
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-1beta (NRG-1beta) is a growth and survival factor in cardiac myocytes. We tested the hypothesis that palmitate alters NRG-1beta signaling and biology in isolated neonatal rat cardiac myocytes. Palmitate treatment inhibited NRG-1beta activation of the PI3-kinase/Akt pathway in myocytes. We found that the pro-apoptotic activity of palmitate was increased by NRG-1beta treatment. The effects of palmitate on NRG-1beta signaling and survival were reversed by the mono-unsaturated fatty acid oleate. Under control conditions NRG-1beta decreases p53 expression in myocytes. In the presence of palmitate, NRG-1beta 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-1beta activates pro-apoptotic, rather than pro-survival signaling in cardiac myocytes.
摘要
饱和脂肪酸棕榈酸盐通过破坏细胞信号传导改变正常细胞功能，这种效应与血脂异常相关的终末器官损伤有关。神经调节蛋白-1β（NRG-1β）是心肌细胞中的一种生长和存活因子。我们检验了以下假设：棕榈酸盐会改变新生大鼠离体心肌细胞中NRG-1β的信号传导和生物学特性。棕榈酸盐处理抑制了心肌细胞中NRG-1β对PI3激酶/Akt途径的激活。我们发现，NRG-1β处理会增加棕榈酸盐的促凋亡活性。单不饱和脂肪酸油酸可逆转棕榈酸盐对NRG-1β信号传导和存活的影响。在对照条件下，NRG-1β可降低心肌细胞中p5３的表达。在棕榈酸盐存在的情况下，NRG-1β导致p53表达增加、bax多聚体形成，同时p53的负调节因子mdm2降解。因此，在棕榈酸盐存在的情况下，NRG-1β在心肌细胞中激活促凋亡信号，而非促存活信号。
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