Kinetic redox proteomic analysis reveals distinct lipopolysaccharide effects, limited by a manganese Superoxide Dismutase mimic

Overproduction of reactive oxygen species and antioxidant superoxide dismutases (SOD1, SOD2) dysregulation contribute to chronic inflammatory bowel disease (IBD) pathogenesis. A kinetic redox proteomic strategy (OcSILAC) was used to explore the lipopolysaccharide (LPS) effect, together with the role of the Mn1 SOD-mimic, in the intestinal HT29-MD2 cellular model. Cysteine oxidation was the main early event of LPS treatment, attenuated over 6 h, as counteracted by rapid response systems on both protein levels (SOD1, NQO1, ALDH1) and post-translational levels (oxidized peroxiredoxins), and a late preponderant increased SOD2 level. Mn1 exerted a potent antioxidant effect, limiting the LPS-induced oxidation and increasing antioxidant enzyme levels, and a variable anti-inflammatory effect attenuating the level of most of the LPS-regulated proteins. Our results reveal the multifaceted LPS effect in intestinal epithelial cells (IECs) and highlight Mn1 as a potential effective anti-oxidant and anti-inflammatory agent for IBD treatment, and a useful tool to explore the oxidation and inflammation interconnection.