Overexpression of CRY1 protects against the development of atherosclerosis via the TLR/NF-κB pathway

Yang, Lei; Chu, Yongchao; Wang, Long'an; Wang, Yuhang; Zhao, Xin; He, Weiming; Zhang, Peirong; Yang, Xianzhi; Liu, Xiaoyu; Tian, Lingling; Li, Bing; Dong, Shujuan; Gao, Chuanyu

doi:10.1016/j.intimp.2015.07.001

Cited by 61 publications

(45 citation statements)

References 25 publications

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“…79 Further, augmented Cry1 expression or Rev-erbβ agonist delivery suppresses atherogenesis in Apoe −/− and Ldlr −/− mice respectively. 93, 94 As discussed, these mouse models have significantly altered lipid metabolism, hematopoiesis and inflammatory state all of which likely contributes to altered atherogenesis. Importantly however, a bone marrow cell specific Clock mutation accelerates atherosclerosis in Apoe −/− mice.…”

Section: Circadian Rhythm In Atherosclerosismentioning

confidence: 99%

Circadian Influence on Metabolism and Inflammation in Atherosclerosis

McAlpine

Świrski

2016

Circulation Research

100

122

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Many aspects of human health and disease display daily rhythmicity. The brain’s suprachiasmic nucleus, which interprets recurring external stimuli, and autonomous molecular networks in peripheral cells together set our biological circadian clock. Disrupted or misaligned circadian rhythms promote multiple pathologies including chronic inflammatory and metabolic diseases like atherosclerosis. Here, we discuss studies suggesting that circadian fluctuations in the vessel wall and in the circulation contribute to atherogenesis. Data from humans and mice indicate that an impaired molecular clock, disturbed sleep and shifting light-dark patterns influence leukocyte and lipid supply in the circulation and alter cellular behavior in atherosclerotic lesions. We propose that a better understanding of both local and systemic circadian rhythms in atherosclerosis will enhance clinical management, treatment and public health policy.

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Section: Circadian Rhythm In Atherosclerosismentioning

confidence: 99%

Circadian Influence on Metabolism and Inflammation in Atherosclerosis

McAlpine

Świrski

2016

Circulation Research

100

122

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“…Induction of Dbp mRNA was used as a marker for Cry1 depletion. Since CRY1 has been also implicated in inhibiting inflammation in various tissues (40,41) and chronic inflammation has been linked to insulin resistance (42,43), we checked the expression of several proinflammatory markers in the liver of Ad-shCry1–injected mice. As shown in Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

DDB1-Mediated CRY1 Degradation Promotes FOXO1-Driven Gluconeogenesis in Liver

et al. 2017

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Targeted protein degradation through ubiquitination is an important step in the regulation of glucose metabolism. Here, we present evidence that the DDB1-CUL4A ubiquitin E3 ligase functions as a novel metabolic regulator that promotes FOXO1-driven hepatic gluconeogenesis. In vivo, hepatocyte-specific Ddb1 deletion leads to impaired hepatic gluconeogenesis in the mouse liver but protects mice from high-fat diet–induced hyperglycemia. Lack of Ddb1 downregulates FOXO1 protein expression and impairs FOXO1-driven gluconeogenic response. Mechanistically, we discovered that DDB1 enhances FOXO1 protein stability via degrading the circadian protein cryptochrome 1 (CRY1), a known target of DDB1 E3 ligase. In the Cry1 depletion condition, insulin fails to reduce the nuclear FOXO1 abundance and suppress gluconeogenic gene expression. Chronic depletion of Cry1 in the mouse liver not only increases FOXO1 protein but also enhances hepatic gluconeogenesis. Thus, we have identified the DDB1-mediated CRY1 degradation as an important target of insulin action on glucose homeostasis.

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“…Previous studies have shown that Cry1 may promote inflammation (Yang et al, ). Deletion of Cry1 and Cry2 increased the number of activated cluster of differentiation (CD)3+ CD69+ T cells and the levels of proinflammatory cytokines including interleukin ( Il )‐ 1β and ‐ and tumor necrosis factor ( Tnf )‐ α leading to induction of arthritis (Hashiramoto et al, ).…”

Section: Discussionmentioning

confidence: 96%

“…Deletion of Cry1 and Cry2 increased the number of activated cluster of differentiation (CD)3+ CD69+ T cells and the levels of proinflammatory cytokines including interleukin ( Il )‐ 1β and ‐ and tumor necrosis factor ( Tnf )‐ α leading to induction of arthritis (Hashiramoto et al, ). Cry1 overexpression in a mouse model of atherosclerosis inhibited the expression of Tnf ‐ α , Il ‐ 1 , and ‐ 6 , and macrophage inflammatory protein 1 as well as of adhesion molecules including intercellular cell adhesion molecule 1, vascular cell adhesion molecule 1, and Sele (Yang et al, ). Consistent with previous studies, our results showed that Cry1 deletion disrupts immune balance, implying that Cry1 regulates the immune response in the testis as in other peripheral circadian oscillators.…”

Section: Discussionmentioning

confidence: 99%

Cry1 deficiency leads to testicular dysfunction and altered expression of genes involved in cell communication, chromatin reorganization, spermatogenesis, and immune response in mouse testis

Xiao

Hao

et al. 2018

Molecular Reproduction Devel

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Cryptochrome (Cry)1 is essential for generating circadian rhythm in central and many peripheral oscillators; however, its role in male reproduction remains unclear. We investigated this question using Cry1 knockout (KO) mice. We found that Cry1 is necessary for normal testicular function: Cry1 deficiency increased testicular germ cell apoptosis and decreased sperm count. A transcriptome analysis showed that the expression levels of 375 genes-including 12 encoding micro (mi)RNAs-were altered in the testis of Cry1 KO mice relative to wild-type controls. A bioinformatics analysis revealed that the differentially expressed genes were related to important biological processes including cell-cell communication, metabolism, chromatin reorganization, spermatogenesis, and the immune response. An integrative analysis of miRNA-mRNA networks suggested that the 12 dysregulated miRNAs may contribute to testis disorders through negative regulation of their target mRNAs expression in testis, and interestingly, all the 12 miRNAs are predicted to target core circadian clock components. These results provide the first evidence of a correlation between dysregulation of Cry1 and male reproductive defects in mice, indicating that Cry1 plays a critical role in maintaining normal testicular function.

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Overexpression of CRY1 protects against the development of atherosclerosis via the TLR/NF-κB pathway

Cited by 61 publications

References 25 publications

Circadian Influence on Metabolism and Inflammation in Atherosclerosis

Circadian Influence on Metabolism and Inflammation in Atherosclerosis

DDB1-Mediated CRY1 Degradation Promotes FOXO1-Driven Gluconeogenesis in Liver

Cry1 deficiency leads to testicular dysfunction and altered expression of genes involved in cell communication, chromatin reorganization, spermatogenesis, and immune response in mouse testis

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