Effects of Manganese Porphyrins on Cellular Sulfur Metabolism

Manganese porphyrins (MnPs), MnTE-2-PyP⁵⁺, MnTnHex-2-PyP⁵⁺ and MnTnBuOE-2-PyP⁵⁺, are superoxide dismutase (SOD) mimetics and form a redox cycle between O₂ and reductants, including ascorbic acid, ultimately producing hydrogen peroxide (H₂O₂). We previously found that MnPs oxidize hydrogen sulfide (H₂S) to polysulfides (PS; H₂S_n, n = 2-6) in buffer. Here, we examine the effects of MnPs for 24 h on H₂S metabolism and PS production in HEK293, A549, HT29 and bone marrow derived stem cells (BMDSC) using H₂S (AzMC, MeRho-AZ) and PS (SSP4) fluorophores. All MnPs decreased intracellular H₂S production and increased intracellular PS. H₂S metabolism and PS production were unaffected by cellular O₂ (5% versus 21% O₂), H₂O₂ or ascorbic acid. We observed with confocal microscopy that mitochondria are a major site of H₂S production in HEK293 cells and that MnPs decrease mitochondrial H₂S production and increase PS in what appeared to be nucleoli and cytosolic fibrillary elements. This supports a role for MnPs in the metabolism of H₂S to PS, the latter serving as both short- and long-term antioxidants, and suggests that some of the biological effects of MnPs may be attributable to sulfur metabolism.