Overexpression of circadian clock protein cryptochrome (CRY) 1 alleviates sleep deprivation-induced vascular inflammation in a mouse model
Overexpression of circadian clock protein cryptochrome (CRY) 1 alleviates sleep deprivation-induced vascular inflammation in a mouse model
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DOI：
10.1016/j.imlet.2014.11.014
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发表时间：
2015-01-01
影响因子：
4.4
通讯作者：
Deng, Yunlong
中科院分区：
文献类型：
--
作者：
Qin, Bing;Deng, Yunlong
有人认为昼夜节律的扰动涉及炎症的调节。但是，在调节睡眠剥夺过程中调节促炎过程中昼夜节律振荡器成分的基本机制仍然很少了解。使用睡眠剥夺小鼠模型，我们在这里表明睡眠剥夺增加了促炎性细胞因子表达的表达，并降低了血管内皮细胞中隐性1（CRY1）的表达。此外，在血管内皮细胞中，包括细胞间粘附分子1，血管细胞粘附分子1和E-选择素的粘附分子在血管内皮细胞中升高，并且通过睡眠剥夺与血管内皮细胞结合的单核细胞也升高。有趣的是，腺病毒载体对小鼠模型中CRY1的过表达显着抑制了炎症细胞因子和粘附分子的表达，NF-kappa B信号途径激活，以及单核细胞与血管内皮细胞的结合。使用荧光素酶报道器测定法，我们发现CRY1可以在体外抑制核因子（NF）-Kappa B的转录活性。随后，我们证明CRY1的过表达抑制了环状腺苷单磷酸（CAMP）的基础浓度，从而导致蛋白激酶A活性降低，从而降低了p65的磷酸化。采取这些结果表明，CRY1的过表达抑制了睡眠剥夺引起的血管炎症，这可能与NF-KAPPA B和CAMP/PKA途径有关。 （c）2014 Elsevier B.V.保留所有权利。
Disturbance of the circadian clock by sleep deprivation has been proposed to be involved in the regulation of inflammation. However, the underlying mechanism of circadian oscillator components in regulating the pro-inflammatory process during sleep deprivation remains poorly understood. Using a sleep deprivation mouse model, we showed here that sleep deprivation increased the expression of pro-inflammatory cytokines expression and decreased the expression of cryptochrome 1 (CRY1) in vascular endothelial cells. Furthermore, the adhesion molecules including intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin were elevated in vascular endothelial cells and the monocytes binding to vascular endothelial cells were also increased by sleep deprivation. Interestingly, overexpression of CRY1 in a mouse model by adenovirus vector significantly inhibited the expression of inflammatory cytokines and adhesion molecules, and NF-kappa B signal pathway activation, as well as the binding of monocytes to vascular endothelial cells. Using a luciferase reporter assay, we found that CRY1 could repress the transcriptional activity of nuclear factor (NF)-kappa B in vitro. Subsequently, we demonstrated that overexpression of CRY1 inhibited the basal concentration of cyclic adenosine monophosphate (cAMP), leading to decreased protein kinase A activity, which resulted in decreased phosphorylation of p65. Taken these results suggested that the overexpression of CRY1 inhibited sleep deprivation-induced vascular inflammation that might be associated with NF-kappa B and cAMP/PKA pathways. (C) 2014 Elsevier B.V. All rights reserved.