Cysteine thiol oxidation on SIRT2 regulates inflammation in obese mice with sepsis.

摘要: Obesity increases morbidity and mortality in acute illnesses such as sepsis septic shock. We showed previously that the early/hyper-inflammatory phase of is exaggerated obese mice with sepsis; sirtuin 2 (SIRT2) modulates inflammation obesity. Evidence suggests obesity associated increased oxidative stress. It unknown whether hyper-inflammation SIRT2 function return. recently SIRT6 oxidation during its glycolytic function. This study tested hypothesis stress direct exaggerate sepsis. Using spleen liver tissue from diet-induced (DIO) we studied oxidized vs. total expression hyper- hypo-inflammation To elucidate mechanism (specific modifications redox-sensitive cysteines) effect on inflammation, performed site-directed mutations cysteines Cys221 Cys224 to serine (C221S C224S), transfected HEK293 cells mutants or WT SIRT2, enzymatic activity NFĸBp65 deacetylation. Finally, mutation LPS-induced using RAW 264.7 macrophages. In an inverse relationship, decreased while was unable deacetylate Mechanistically, both C224S) show (1) activity, (2) deacetylation NFĸBp65, (3) anti-inflammatory response LPS SIRT2. Direct hyper-inflammatory via redox sensitive cysteines.