Abstract:
:Activation of the inflammatory response is accompanied by a metabolic shift to aerobic glycolysis. Here we identify histone deacetylase 4 (HDAC4) as a new component of the immunometabolic program. We show that HDAC4 is required for efficient inflammatory cytokine production activated by lipopolysaccharide (LPS). Surprisingly, prolonged LPS treatment leads to HDAC4 degradation. LPS-induced HDAC4 degradation requires active glycolysis controlled by GSK3β and inducible nitric oxide synthase (iNOS). Inhibition of GSK3β or iNOS suppresses nitric oxide (NO) production, glycolysis, and HDAC4 degradation. We present evidence that sustained glycolysis induced by LPS treatment activates caspase-3, which cleaves HDAC4 and triggers its degradation. Of importance, a caspase-3-resistant mutant HDAC4 escapes LPS-induced degradation and prolongs inflammatory cytokine production. Our findings identify the GSK3β-iNOS-NO axis as a critical signaling cascade that couples inflammation to metabolic reprogramming and a glycolysis-driven negative feedback mechanism that limits inflammatory response by triggering HDAC4 degradation.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Wang B,Liu TY,Lai CH,Rao YH,Choi MC,Chi JT,Dai JW,Rathmell JC,Yao TPdoi
10.1091/mbc.E13-12-0757subject
Has Abstractpub_date
2014-11-01 00:00:00pages
3300-7issue
21eissn
1059-1524issn
1939-4586pii
mbc.E13-12-0757journal_volume
25pub_type
杂志文章abstract::When demembranated sperm nuclei are placed in a Xenopus egg extract, they become surrounded by a nuclear envelope and then swell to form morphologically typical pronuclei. Granules ranging from < 1.0 to approximately 3.0 microns in diameter appear within such nuclei. Bell et al. identified four nucleolar proteins in t...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.5.6.633
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journal_title:Molecular biology of the cell
pub_type: 杂志文章
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journal_title:Molecular biology of the cell
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular biology of the cell
pub_type: 杂志文章
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更新日期:2018-03-15 00:00:00
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journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.11.3.1061
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journal_title:Molecular biology of the cell
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更新日期:2008-04-01 00:00:00
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journal_title:Molecular biology of the cell
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doi:10.1091/mbc.e06-09-0843
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journal_title:Molecular biology of the cell
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journal_title:Molecular biology of the cell
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