Manganese porphyrin-based SOD mimetics produce polysulfides from hydrogen sulfide

Kenneth R. Olson, Yan Gao, Faihaan Arif, Shivali Patel, Xiaotong Yuan, Varun Mannam, Scott Howard, Ines Batinic-Haberle, Jon Fukuto, Magdalena Minnion, Martin Feelisch, Karl D. Straub

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Manganese-centered porphyrins (MnPs), MnTE-2-PyP5+ (MnTE), MnTnHex-2-PyP5+ (MnTnHex), and MnTnBuOE-2-PyP5+ (MnTnBuOE) have received considerable attention because of their ability to serve as superoxide dismutase (SOD) mimetics thereby producing hydrogen peroxide (H2O2), and oxidants of ascorbate and simple aminothiols or protein thiols. MnTE-2-PyP5+ and MnTnBuOE-2-PyP5+ are now in five Phase II clinical trials warranting further exploration of their rich redox-based biology. Previously, we reported that SOD is also a sulfide oxidase catalyzing the oxidation of hydrogen sulfide (H2S) to hydrogen persulfide (H2S2) and longer-chain polysulfides (H2Sn, n = 3–7). We hypothesized that MnPs may have similar actions on sulfide metabolism. H2S and polysulfides were monitored in fluorimetric assays with 7-azido-4-methylcoumarin (AzMC) and 3,6-di(O-thiosalicyl)fluorescein (SSP4), respectively, and specific polysulfides were further identified by mass spectrometry. MnPs concentration-dependently consumed H2S and produced H2S2 and subsequently longer-chain polysulfides. This reaction appeared to be O2-dependent. MnP absorbance spectra exhibited wavelength shifts in the Soret and Q bands characteristic of sulfide-mediated reduction of Mn. Taken together, our results suggest that MnPs can become efficacious activators of a variety of cytoprotective processes by acting as sulfide oxidation catalysts generating per/polysulfides.

Original languageEnglish (US)
Article number639
JournalAntioxidants
Volume8
Issue number12
DOIs
StatePublished - Dec 2019

Keywords

  • Antioxidants
  • BMX-001
  • HS
  • Mn porphyrins
  • Reactive oxygen species
  • Reactive sulfur species

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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    Olson, K. R., Gao, Y., Arif, F., Patel, S., Yuan, X., Mannam, V., Howard, S., Batinic-Haberle, I., Fukuto, J., Minnion, M., Feelisch, M., & Straub, K. D. (2019). Manganese porphyrin-based SOD mimetics produce polysulfides from hydrogen sulfide. Antioxidants, 8(12), [639]. https://doi.org/10.3390/antiox8120639