國家衛生研究院 NHRI:Item 3990099045/7981
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    題名: Necrosis-driven systemic immune response alters SAM metabolism through the FOXO-GNMT axis
    作者: Obata, F;Kuranaga, E;Tomioka, K;Ming, M;Takeishi, A;Chen, CH;Soga, T;Miura, M
    貢獻者: Institute of Molecular and Genomic Medicine
    摘要: Sterile inflammation triggered by endogenous factors is thought to contribute to the pathogenesis of acute and chronic inflammatory diseases. Here, we demonstrate that apoptosis-deficient mutants spontaneously develop a necrosis-driven systemic immune response in Drosophila and provide an in vivo model for studying the organismal response to sterile inflammation. Metabolomic analysis of hemolymph from apoptosis-deficient mutants revealed increased sarcosine and reduced S-adenosyl-methionine (SAM) levels due to glycine N-methyltransferase (Gnmt) upregulation. We showed that Gnmt was elevated in response to Toll activation induced by the local necrosis of wing epidermal cells. Necrosis-driven inflammatory conditions induced dFoxO hyperactivation, leading to an energy-wasting phenotype. Gnmt was cell-autonomously upregulated by dFoxO in the fat body as a possible rheostat for controlling energy loss, which functioned during fasting as well as inflammatory conditions. We propose that the dFoxO-Gnmt axis is essential for the maintenance of organismal SAM metabolism and energy homeostasis.
    日期: 2014-05
    關聯: Cell Reports. 2014 May;7(3):821-833.
    Link to: http://dx.doi.org/10.1016/j.celrep.2014.03.046
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2211-1247&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000335560900023
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84899935245
    顯示於類別:[陳俊宏] 期刊論文

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