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标题:Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders
时间:2019-11-19 23:08:19
DOI:10.1016/j.cellsig.2013.06.007
作者:Kauppinen, Anu; Suuronen, Tiina; Ojala, Johanna
关键词:AGRP, agouti-related protein; AMPK, AMP-activated protein kinase; AP-1, activator protein-1; BCL10, B-cell lymphoma/leukemia-10; CIITA, class II, major histocompatibility complex, transactivator; DHA, docosahexaenoic acid; E2F1, transcription factor E2F1; EPA, eicosapentaenoic acid; ERK, extracellular signal-regulated kinase; FoxO, Forkhead box O protein; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; HIC1, hypermethylated in cancer-1; HIF, hypoxia-inducible factor; IκBα, inhibitor of κB pr
出版源: Cellular Signalling ,25 (10) :1939-1948
摘要:Recent studies have indicated that the regulation of innate immunity and energy metabolism are connected together through an antagonistic crosstalk between NF-κB and SIRT1 signaling pathways. NF-κB signaling has a major role in innate immunity defense while SIRT1 regulates the oxidative respiration and cellular survival. However, NF-κB signaling can stimulate glycolytic energy flux during acute inflammation, whereas SIRT1 activation inhibits NF-κB signaling and enhances oxidative metabolism and the resolution of inflammation. SIRT1 inhibits NF-κB signaling directly by deacetylating the p65 subunit of NF-κB complex. SIRT1 stimulates oxidative energy production via the activation of AMPK, PPARα and PGC-1α and simultaneously, these factors inhibit NF-κB signaling and suppress inflammation. On the other hand, NF-κB signaling down-regulates SIRT1 activity through the expression of miR-34a, IFNγ, and reactive oxygen species. The inhibition of SIRT1 disrupts oxidative energy metabolism and stimulates the NF-κB-induced inflammatory responses present in many chronic metabolic and age-related diseases. We will examine the molecular mechanisms of the antagonistic signaling between NF-κB and SIRT1 and describe how this crosstalk controls inflammatory process and energy metabolism. In addition, we will discuss how disturbances in this signaling crosstalk induce the appearance of chronic inflammation in metabolic diseases.
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页数:11 PAGES
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目录:
  • Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders
    • 1. Introduction
    • 2. Antagonistic crosstalk between SIRT1 and NF-κB
      • 2.1. SIRT1 inhibits NF-κB signaling
      • 2.2. NF-κB inhibits SIRT1 expression and signaling
      • 2.3. Antagonistic crosstalk with other signaling pathways
    • 3. Signaling crosstalk between NF-κB and SIRT1 controls inflammatory phases and energy metabolic supply
    • 4. Disturbances in the crosstalk between NF-κB and SIRT1 induce metabolic disorders
    • 5. Conclusions
    • Acknowledgments
    • References

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