Iron increases manganese superoxide dismutase activity in intestinal epithelial cells

Manganese superoxide dismutase (MnSOD) is an enzyme that functions in the mitochondria to detoxify superoxide radicals. MnSOD is low or absent in tumor cells and may act as a tumor suppressor. MnSOD is induced by inflammatory cytokines such as tumor necrosis factor alpha (TNF), potentially as a protective measure for host cells. Previous studies have shown that MnSOD activity decreases during early stages of colon carcinogenesis. Studies using a rodent model showed that diets high in iron also decreased the activity of this enzyme. The present study was designed to use a cell culture model to further investigate the effect of supplemental iron on MnSOD production and activity. Rat intestinal epithelial cells (IEC-6) were cultured in media supplemented with either linoleic acid or eicosapentaenoic acid and iron. The effect of iron on lipid peroxidation products and rate of proliferation was determined. MnSOD protein levels and activity were determined in the lipid and iron treated cells following treatment with TNF. Results showed that lipid peroxidation products increased with iron supplementation. Iron supplementation did not alter cell proliferation. Iron supplementation increased MnSOD protein levels and activity in the non-TNF treated cells but did not influence the ability of TNF to induce MnSOD in IEC-6 cells. Findings indicate that supplemental iron may increase MnSOD due to increased oxidative stress but does not compromise the ability of inflammatory mediators to further increase the activity of this enzyme.