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Metabolism of hydrogen sulfide (H2S) and production of Reactive Sulfur Species (RSS) by superoxide dismutase

Metabolism of hydrogen sulfide (H2S) and production of Reactive Sulfur Species (RSS) by superoxide dismutase
Metabolism of hydrogen sulfide (H2S) and production of Reactive Sulfur Species (RSS) by superoxide dismutase

Reactive sulfur species (RSS) such as H2S, HS•, H2Sn, (n = 2-7) and HS2•- are chemically similar to H2O and the reactive oxygen species (ROS) HO•, H2O2, O2•- and act on common biological effectors. RSS were present in evolution long before ROS, and because both are metabolized by catalase it has been suggested that "antioxidant" enzymes originally evolved to regulate RSS and may continue to do so today. Here we examined RSS metabolism by Cu/Zn superoxide dismutase (SOD) using amperometric electrodes for dissolved H2S, a polysulfide-specific fluorescent probe (SSP4), and mass spectrometry to identify specific polysulfides (H2S2-H2S5). H2S was concentration- and oxygen-dependently oxidized by 1μM SOD to polysulfides (mainly H2S2, and to a lesser extent H2S3 and H2S5) with an EC50 of approximately 380μM H2S. H2S concentrations > 750μM inhibited SOD oxidation (IC50 = 1.25mM) with complete inhibition when H2S > 1.75mM. Polysulfides were not metabolized by SOD. SOD oxidation preferred dissolved H2S over hydrosulfide anion (HS-), whereas HS- inhibited polysulfide production. In hypoxia, other possible electron donors such as nitrate, nitrite, sulfite, sulfate, thiosulfate and metabisulfite were ineffective. Manganese SOD also catalyzed H2S oxidation to form polysulfides, but did not metabolize polysulfides indicating common attributes of these SODs. These experiments suggest that, unlike the well-known SOD-mediated dismutation of two O2•- to form H2O2 and O2, SOD catalyzes a reaction using H2S and O2 to form persulfide. These can then combine in various ways to form polysulfides and sulfur oxides. It is also possible that H2S (or polysulfides) interact/react with SOD cysteines to affect catalytic activity or to directly contribute to sulfide metabolism. Our studies suggest that H2S metabolism by SOD may have been an ancient mechanism to detoxify sulfide or to regulate RSS and along with catalase may continue to do so in contemporary organisms.

Journal Article
2213-2317
74-85
Olson, Kenneth R.
82b73d34-60b6-4915-9328-c50805bea090
Gao, Yan
97e17892-445d-4dff-930f-294cea66e433
Arif, Faihaan
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Arora, Kanika
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Patel, Shivali
b6a7e388-0300-41e2-9645-a3810f0950d7
DeLeon, Eric R.
5d67047e-10c2-4285-9ae6-7221c594229e
Sutton, Thomas R.
dbc4cb4f-cab0-46ee-b911-8945f50563cd
Feelisch, Martin
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Cortese-Krott, Miriam M.
7dc9b44c-847c-4196-8866-a3cc0c1dc357
Straub, Karl D.
5cc49000-f71b-49ec-8e00-8fc21e29d293
Olson, Kenneth R.
82b73d34-60b6-4915-9328-c50805bea090
Gao, Yan
97e17892-445d-4dff-930f-294cea66e433
Arif, Faihaan
5de29e3c-d981-4935-a68f-5dc861cb5526
Arora, Kanika
72c7a3f7-d437-43ce-b9a5-337c35a01464
Patel, Shivali
b6a7e388-0300-41e2-9645-a3810f0950d7
DeLeon, Eric R.
5d67047e-10c2-4285-9ae6-7221c594229e
Sutton, Thomas R.
dbc4cb4f-cab0-46ee-b911-8945f50563cd
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Cortese-Krott, Miriam M.
7dc9b44c-847c-4196-8866-a3cc0c1dc357
Straub, Karl D.
5cc49000-f71b-49ec-8e00-8fc21e29d293

Olson, Kenneth R., Gao, Yan, Arif, Faihaan, Arora, Kanika, Patel, Shivali, DeLeon, Eric R., Sutton, Thomas R., Feelisch, Martin, Cortese-Krott, Miriam M. and Straub, Karl D. (2018) Metabolism of hydrogen sulfide (H2S) and production of Reactive Sulfur Species (RSS) by superoxide dismutase. Redox Biology, 15, 74-85. (doi:10.1016/j.redox.2017.11.009).

Record type: Article

Abstract

Reactive sulfur species (RSS) such as H2S, HS•, H2Sn, (n = 2-7) and HS2•- are chemically similar to H2O and the reactive oxygen species (ROS) HO•, H2O2, O2•- and act on common biological effectors. RSS were present in evolution long before ROS, and because both are metabolized by catalase it has been suggested that "antioxidant" enzymes originally evolved to regulate RSS and may continue to do so today. Here we examined RSS metabolism by Cu/Zn superoxide dismutase (SOD) using amperometric electrodes for dissolved H2S, a polysulfide-specific fluorescent probe (SSP4), and mass spectrometry to identify specific polysulfides (H2S2-H2S5). H2S was concentration- and oxygen-dependently oxidized by 1μM SOD to polysulfides (mainly H2S2, and to a lesser extent H2S3 and H2S5) with an EC50 of approximately 380μM H2S. H2S concentrations > 750μM inhibited SOD oxidation (IC50 = 1.25mM) with complete inhibition when H2S > 1.75mM. Polysulfides were not metabolized by SOD. SOD oxidation preferred dissolved H2S over hydrosulfide anion (HS-), whereas HS- inhibited polysulfide production. In hypoxia, other possible electron donors such as nitrate, nitrite, sulfite, sulfate, thiosulfate and metabisulfite were ineffective. Manganese SOD also catalyzed H2S oxidation to form polysulfides, but did not metabolize polysulfides indicating common attributes of these SODs. These experiments suggest that, unlike the well-known SOD-mediated dismutation of two O2•- to form H2O2 and O2, SOD catalyzes a reaction using H2S and O2 to form persulfide. These can then combine in various ways to form polysulfides and sulfur oxides. It is also possible that H2S (or polysulfides) interact/react with SOD cysteines to affect catalytic activity or to directly contribute to sulfide metabolism. Our studies suggest that H2S metabolism by SOD may have been an ancient mechanism to detoxify sulfide or to regulate RSS and along with catalase may continue to do so in contemporary organisms.

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Accepted/In Press date: 8 November 2017
e-pub ahead of print date: 20 November 2017
Published date: May 2018
Additional Information: Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Keywords: Journal Article

Identifiers

Local EPrints ID: 417267
URI: https://eprints.soton.ac.uk/id/eprint/417267
ISSN: 2213-2317
PURE UUID: 4d97d24b-4e49-488d-9d29-a3655f745a28
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 26 Jan 2018 17:30
Last modified: 01 May 2018 16:30

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Contributors

Author: Kenneth R. Olson
Author: Yan Gao
Author: Faihaan Arif
Author: Kanika Arora
Author: Shivali Patel
Author: Eric R. DeLeon
Author: Thomas R. Sutton
Author: Martin Feelisch ORCID iD
Author: Miriam M. Cortese-Krott
Author: Karl D. Straub

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