Novel Nongenomic Signaling by Glucocorticoid May Involve Changes to Liver Membrane Order in Rainbow Trout
Novel Nongenomic Signaling by Glucocorticoid May Involve Changes to Liver Membrane Order in Rainbow Trout
复制标题
DOI：
10.1371/journal.pone.0046859
复制
发表时间：
2012-10-08
期刊：
影响因子：
3.7
通讯作者：
Vijayan, Mathilakath M.
中科院分区：
文献类型：
--
作者：
Dindia, Laura;Murray, Josh;Vijayan, Mathilakath M.
压力引起的糖皮质激素升高是脊椎动物中高度保守的反应。这有利于应激适应，作用模式涉及细胞内糖皮质激素受体的激活，从而导致靶基因表达的调节。然而，这种基因组效应作用缓慢，因此糖皮质激素在应激快速反应中的作用尚不清楚。在这里，我们发现皮质醇（硬骨鱼中的主要糖皮质激素）的应激水平可在体外迅速使虹鳟鱼（Oncorhynchus mykiss）肝脏质膜流化。这涉及将类固醇掺入脂质结构域，因为皮质醇与膜不可渗透的肽部分偶联，不会影响膜秩序。研究证实，皮质醇而非性类固醇可以增加肝脏质膜的流动性。原子力显微镜揭示了皮质醇介导的膜表面形貌和粘弹性的变化，证实了膜顺序的变化。用皮质醇应激水平处理鳟鱼肝细胞会导致细胞信号传导途径的调节，包括 10 分钟内假定的 PKA、PKC 和 AKT 底物蛋白的磷酸化状态。在皮质醇存在的情况下，蛋白激酶的磷酸化与苯甲醇（一种已知的膜流化剂）所观察到的磷酸化一致。我们的结果表明，由应激源诱导的糖皮质激素升高引发的质膜特性的生物物理变化，充当非特异性应激反应，并可能快速调节急性应激信号通路。
Stress-induced glucocorticoid elevation is a highly conserved response among vertebrates. This facilitates stress adaptation and the mode of action involves activation of the intracellular glucocorticoid receptor leading to the modulation of target gene expression. However, this genomic effect is slow acting and, therefore, a role for glucocorticoid in the rapid response to stress is unclear. Here we show that stress levels of cortisol, the primary glucocorticoid in teleosts, rapidly fluidizes rainbow trout (Oncorhynchus mykiss) liver plasma membranes in vitro. This involved incorporation of the steroid into the lipid domains, as cortisol coupled to a membrane impermeable peptide moiety, did not affect membrane order. Studies confirmed that cortisol, but not sex steroids, increases liver plasma membrane fluidity. Atomic force microscopy revealed cortisol-mediated changes to membrane surface topography and viscoelasticity confirming changes to membrane order. Treating trout hepatocytes with stress levels of cortisol led to the modulation of cell signaling pathways, including the phosphorylation status of putative PKA, PKC and AKT substrate proteins within 10 minutes. The phosphorylation by protein kinases in the presence of cortisol was consistent with that seen with benzyl alcohol, a known membrane fluidizer. Our results suggest that biophysical changes to plasma membrane properties, triggered by stressor-induced glucocorticoid elevation, act as a nonspecific stress response and may rapidly modulate acute stress-signaling pathways.