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