کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2041819 1073174 2014 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
پیش نمایش صفحه اول مقاله
Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis
چکیده انگلیسی


• Defective fly wing cell apoptosis in dark mutants induces a systemic immune response
• Metabolomics of dark mutants reveals a reduction in SAM levels due to Gnmt elevation
• Toll activation-induced Gnmt expression is mediated by dFoxO in the fat body
• Gnmt may be induced as a protective mechanism against wasting

SummarySterile 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.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 7, Issue 3, 8 May 2014, Pages 821–833
نویسندگان
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