Effects of manganese porphyrins on cellular sulfur metabolism

Kenneth R. Olson, Yan Gao, Andrea K. Steiger, Michael D. Pluth, Charles R. Tessier, Troy A. Markel, David Boone, Robert V. Stahelin, Ines Batinic-Haberle, Karl D. Straubg

Research output: Contribution to journalArticle

Abstract

Manganese porphyrins (MnPs),MnTE-2-PyP5+, MnTnHex-2-PyP5+ and MnTnBuOE-2-PyP5+, are superoxide dismutase (SOD) mimetics and forma 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 metabolismand 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.

Original languageEnglish (US)
Article number980
JournalMolecules
Volume25
Issue number4
DOIs
StatePublished - Feb 22 2020

Keywords

  • Antioxidants;Mn porphyrins
  • HS
  • Polysulfides
  • ROS
  • Reactive sulfide species
  • SODmimetics

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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  • Cite this

    Olson, K. R., Gao, Y., Steiger, A. K., Pluth, M. D., Tessier, C. R., Markel, T. A., Boone, D., Stahelin, R. V., Batinic-Haberle, I., & Straubg, K. D. (2020). Effects of manganese porphyrins on cellular sulfur metabolism. Molecules, 25(4), [980]. https://doi.org/10.3390/molecules25040980