Intracellular methylglyoxal accumulation in classically activated mouse macrophages is mediated by HIF-1α.

ABSTRACT: Approximately one million cases of sepsis in the United States occur annually. The early phase of sepsis features dramatic changes in host metabolism and inflammation. While examining the effects of metabolic pathways on inflammation, we discovered that the highly reactive glycolytic metabolite, methylglyoxal (MG), accumulates intracellularly during classical activation of macrophages. Herein, we explored the role of glycolysis and the master regulator of glycolysis, Hypoxia-Inducing Factor-1α (HIF-1α), in inflammation and MG accumulation in mouse and human macrophages. To determine how HIF-1α regulates the inflammatory response of macrophages, we correlated HIF-1α stabilization with proinflammatory gene expression and MG-adduct accumulation in WT vs HIF1a-deficient macrophages treated wit

SUBMITTER: Prantner D 

PROVIDER: S-EPMC12854256 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature