Effects of Manganese Porphyrins on Cellular Sulfur Metabolism

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