Manganese porphyrin-based SOD mimetics produce polysulfides from hydrogen sulfide
Manganese porphyrin-based SOD mimetics produce polysulfides from hydrogen sulfide
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.
1-19
Olson, Kenneth R.
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Gao, Yan
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Arif, Faihaan
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Patel, Shivali
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Yuan, Xiaotong
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Mannam, Varun
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Howard, Scott
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Batinic-Haberle, Ines
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Fukuto, Jon
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Minnion, Magdalena
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Feelisch, Martin
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Straub, Karl D.
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December 2019
Olson, Kenneth R.
82b73d34-60b6-4915-9328-c50805bea090
Gao, Yan
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Arif, Faihaan
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Patel, Shivali
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Yuan, Xiaotong
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Mannam, Varun
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Howard, Scott
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Batinic-Haberle, Ines
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Fukuto, Jon
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Minnion, Magdalena
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Feelisch, Martin
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Straub, Karl D.
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Olson, Kenneth R., Gao, Yan, Arif, Faihaan, Patel, Shivali, Yuan, Xiaotong, Mannam, Varun, Howard, Scott, Batinic-Haberle, Ines, Fukuto, Jon, Minnion, Magdalena, Feelisch, Martin and Straub, Karl D.
(2019)
Manganese porphyrin-based SOD mimetics produce polysulfides from hydrogen sulfide.
Antioxidants, 8 (12), .
(doi:10.3390/antiox8120639).
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.
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antioxidants-08-00639 (1)
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Accepted/In Press date: 6 December 2016
e-pub ahead of print date: 12 December 2019
Published date: December 2019
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Local EPrints ID: 439471
URI: http://eprints.soton.ac.uk/id/eprint/439471
ISSN: 2076-3921
PURE UUID: 2d6513e5-0eea-4304-b4dc-39c209c527e8
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Date deposited: 23 Apr 2020 16:54
Last modified: 17 Mar 2024 03:27
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Contributors
Author:
Kenneth R. Olson
Author:
Yan Gao
Author:
Faihaan Arif
Author:
Shivali Patel
Author:
Xiaotong Yuan
Author:
Varun Mannam
Author:
Scott Howard
Author:
Ines Batinic-Haberle
Author:
Jon Fukuto
Author:
Magdalena Minnion
Author:
Karl D. Straub
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