糖皮质激素引起的新的非基因组信号转导可能涉及虹鳟〈动物〉<动物>肝膜有序性的改变
Novel Nongenomic Signaling by Glucocorticoid May Involve Changes to Liver Membrane Order in Rainbow Trout
摘要：
应激诱导的糖皮质激素升高是脊椎动物中高度保守的反应。这促进了应激适应，并且作用模式涉及细胞内糖皮质激素受体的激活，导致靶基因表达的调节。然而，这种基因组效应是缓慢作用的，因此，糖皮质激素在对应激的快速反应中的作用尚不清楚。在这里，我们表明，应激水平的皮质醇，主要的糖皮质激素在硬骨鱼，迅速流化虹鳟〈动物〉<动物>（虹鳟鱼mykiss）肝质膜在体外。这涉及到的类固醇纳入脂质结构域，皮质醇耦合到膜不可渗透的肽部分，不影响膜秩序。研究证实，皮质醇，而不是性类固醇，增加肝质膜流动性。原子力显微镜显示皮质醇介导的变化，膜表面形貌和粘弹性确认膜秩序的变化。用应激水平的皮质醇处理鳟鱼肝细胞导致细胞信号转导通路的调节，包括10分钟内推定的PKA、PKC和AKT底物蛋白的磷酸化状态。皮质醇存在下蛋白激酶的磷酸化与苯甲醇（一种已知的膜流化剂）的磷酸化一致。我们的研究结果表明，生物物理的质膜特性的变化，引发应激诱导的糖皮质激素升高，作为一种非特异性的应激反应，并可能迅速调节急性应激信号通路。
英文摘要：
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.
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