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; H2Sn, 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.
Olson, KR; Gao, Y; Steiger, AK; Pluth, MD; Tessier, CR; Markel, TA; Boone, D; Stahelin, RV; Batinic-Haberle, I; Straubg, KD
Volume / Issue
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)