Effects of Manganese Porphyrins on Cellular Sulfur Metabolism.

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