title: Overexpression of circadian clock protein cryptochrome (CRY) 1 alleviates sleep deprivation-induced vascular inflammation in a mouse model.
abstract: 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-κB 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)-κB 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 together, these results suggested that the overexpression of CRY1 inhibited sleep deprivation-induced vascular inflammation that might be associated with NF-κB and cAMP/PKA pathways.
authors.affiliation: Psychosomatic Health Institute, the 3rd Xiangya Hospital, Central South University, Changsha, Hunan 410013, PR China; Henan Medical College, Zhengzhou, Henan 451191, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Qin
authors.affiliation: Psychosomatic Health Institute, the 3rd Xiangya Hospital, Central South University, Changsha, Hunan 410013, PR China. Electronic address: 67938996@qq.com.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Deng
mesh_terms: D000818:Animals; D056931:Cryptochromes / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000242:Cyclic AMP / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D012892:Sleep Deprivation / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014657:Vasculitis / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control
chemical_list: C538964:Cry1 protein, mouse; D056931:Cryptochromes; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Cryptochrome; NF-κB; PKA; Sleep deprivation; Vascular inflammation; cAMP