Glutathionylation of Pyruvate Dehydrogenase Complex E2 and Inflammatory Cytokine Production During Acute Inflammation Are Magnified By Mitochondrial Oxidative Stress.

ABSTRACT: Lipopolysaccharide (LPS) is a known inducer of inflammatory signaling which triggers generation of reactive oxygen species (ROS) and cell death in responsive cells like THP-1 promonocytes and freshly isolated human monocytes. A key LPS-responsive metabolic pivot point is the 9 megadalton mitochondrial pyruvate dehydrogenase complex (PDC), which provides pyruvate dehydrogenase (E1), lipoamide-linked transacetylase (E2) and lipoamide dehydrogenase (E3) activities to produce acetyl-CoA from pyruvate. While phosphorylation-dependent decreases in PDC activity following LPS treatment or sepsis have been deeply investigated, redox-linked processes have received less attention. Data presented here demonstrate that LPS-induced reversible oxidation within PDC occurs in PDCE2 in both THP-1 cells and

SUBMITTER: Long DL 

PROVIDER: S-EPMC9900926 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature