Molecular and Cellular Endocrinology ( IF 3.8 ) Pub Date : 2020-10-29 , DOI: 10.1016/j.mce.2020.111067 Chinmayee Das 1 , Erin Faught 1 , Mathilakath M Vijayan 1
Glucocorticoids (GCs) play a role in stress coping by activating the glucocorticoid receptor (GR), a ligand-bound transcription factor. GCs also exert rapid effects that are nongenomic by modulating second messenger signaling, including Ca2+. However, the mechanism of action of GCs in modulating cytoplasmic free calcium level ([Ca2+]i) is unclear. We hypothesized that cortisol increases ([Ca2+]i) in zebrafish (Danio rerio) muscle, and this is independent of GR activation. Indeed, cortisol rapidly stimulated ([Ca2+]i) rise in the developing trunk muscle (DTM), and this response was not abolished in the GR knockout zebrafish. The rapid cortisol-induced ([Ca2+]i) rise was reduced with EGTA, and completely abolished by the pharmacological inhibition of the calcium release-activated calcium channel (CRACC). Also, cortisol stimulation rapidly increased the expression of Orai1, the pore forming protein subunit of CRACC, in the DTM. Altogether, rapid nongenomic action of cortisol on muscle function may involve Ca2+ signaling by CRACC gating in zebrafish.
中文翻译:
皮质醇迅速刺激斑马鱼正在发育的躯干肌肉中的钙波
糖皮质激素 (GC) 通过激活糖皮质激素受体 (GR)(一种配体结合转录因子)在压力应对中发挥作用。GC 还通过调节第二信使信号(包括 Ca 2+ )发挥非基因组的快速作用。然而,GCs 在调节细胞质游离钙水平 ([Ca 2+ ]i) 中的作用机制尚不清楚。我们假设斑马鱼 ( Danio rerio ) 肌肉中的皮质醇增加 ([Ca 2+ ]i) ,这与 GR 激活无关。事实上,皮质醇在发育中的躯干肌肉 (DTM) 中迅速刺激 ([Ca 2+ ]i) 上升,而这种反应在 GR 敲除斑马鱼中并未消除。快速皮质醇诱导的([Ca 2+]i) 升高被 EGTA 降低,并被钙释放激活钙通道 (CRACC) 的药理学抑制完全消除。此外,皮质醇刺激迅速增加了 Orai1(CRACC 的成孔蛋白亚基)在 DTM 中的表达。总之,皮质醇对肌肉功能的快速非基因组作用可能涉及斑马鱼 CRACC 门控的Ca 2+信号传导。