Effects of Manganese Porphyrins on Cellular Sulfur Metabolism
Manganese porphyrins (MnPs), MnTE-2-PyP<sup>5+</sup>, MnTnHex-2-PyP<sup>5+</sup> and MnTnBuOE-2-PyP<sup>5+</sup>, are superoxide dismutase (SOD) mimetics and form a redox cycle between O<sub>2</sub> and reductants, including ascorbic acid, ultimately p...
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doaj-175883133928472f8a1e4bd315c8543f2020-11-25T03:19:30ZengMDPI AGMolecules1420-30492020-02-0125498010.3390/molecules25040980molecules25040980Effects of Manganese Porphyrins on Cellular Sulfur MetabolismKenneth R. Olson0Yan Gao1Andrea K. Steiger2Michael D. Pluth3Charles R. Tessier4Troy A. Markel5David Boone6Robert V. Stahelin7Ines Batinic-Haberle8Karl D. Straubg9Indiana University School of Medicine-South Bend Center, South Bend, IN 46617, USAIndiana University School of Medicine-South Bend Center, South Bend, IN 46617, USADepartment of Chemistry and Biochemistry, University of Oregon, Eugene, OR 97403, USADepartment of Chemistry and Biochemistry, University of Oregon, Eugene, OR 97403, USAIndiana University School of Medicine-South Bend Center, South Bend, IN 46617, USAIndiana University School of Medicine, Riley Hospital for Children at IU Health, 705 Riley Hospital Dr, RI 2500, Indianapolis, IN 46202, USAIndiana University School of Medicine-South Bend Center, South Bend, IN 46617, USADepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USADepartment of Radiation Oncology, School of Medicine, Duke University, Durham, NC 27710, USACentral Arkansas Veteran’s Healthcare System, Little Rock, AR 72205, USAManganese porphyrins (MnPs), MnTE-2-PyP<sup>5+</sup>, MnTnHex-2-PyP<sup>5+</sup> and MnTnBuOE-2-PyP<sup>5+</sup>, are superoxide dismutase (SOD) mimetics and form a redox cycle between O<sub>2</sub> and reductants, including ascorbic acid, ultimately producing hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). We previously found that MnPs oxidize hydrogen sulfide (H<sub>2</sub>S) to polysulfides (PS; H<sub>2</sub>S<sub>n</sub>, n = 2−6) in buffer. Here, we examine the effects of MnPs for 24 h on H<sub>2</sub>S metabolism and PS production in HEK293, A549, HT29 and bone marrow derived stem cells (BMDSC) using H<sub>2</sub>S (AzMC, MeRho-AZ) and PS (SSP4) fluorophores. All MnPs decreased intracellular H<sub>2</sub>S production and increased intracellular PS. H<sub>2</sub>S metabolism and PS production were unaffected by cellular O<sub>2</sub> (5% versus 21% O<sub>2</sub>), H<sub>2</sub>O<sub>2</sub> or ascorbic acid. We observed with confocal microscopy that mitochondria are a major site of H<sub>2</sub>S production in HEK293 cells and that MnPs decrease mitochondrial H<sub>2</sub>S production and increase PS in what appeared to be nucleoli and cytosolic fibrillary elements. This supports a role for MnPs in the metabolism of H<sub>2</sub>S 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.https://www.mdpi.com/1420-3049/25/4/980reactive sulfide speciesrosantioxidantsmn porphyrinssod mimeticsh<sub>2</sub>spolysulfides |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Effects of Manganese Porphyrins on Cellular Sulfur Metabolism Molecules reactive sulfide species ros antioxidants mn porphyrins sod mimetics h<sub>2</sub>s polysulfides |
author_facet |
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 |
author_sort |
Kenneth R. Olson |
title |
Effects of Manganese Porphyrins on Cellular Sulfur Metabolism |
title_short |
Effects of Manganese Porphyrins on Cellular Sulfur Metabolism |
title_full |
Effects of Manganese Porphyrins on Cellular Sulfur Metabolism |
title_fullStr |
Effects of Manganese Porphyrins on Cellular Sulfur Metabolism |
title_full_unstemmed |
Effects of Manganese Porphyrins on Cellular Sulfur Metabolism |
title_sort |
effects of manganese porphyrins on cellular sulfur metabolism |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2020-02-01 |
description |
Manganese porphyrins (MnPs), MnTE-2-PyP<sup>5+</sup>, MnTnHex-2-PyP<sup>5+</sup> and MnTnBuOE-2-PyP<sup>5+</sup>, are superoxide dismutase (SOD) mimetics and form a redox cycle between O<sub>2</sub> and reductants, including ascorbic acid, ultimately producing hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). We previously found that MnPs oxidize hydrogen sulfide (H<sub>2</sub>S) to polysulfides (PS; H<sub>2</sub>S<sub>n</sub>, n = 2−6) in buffer. Here, we examine the effects of MnPs for 24 h on H<sub>2</sub>S metabolism and PS production in HEK293, A549, HT29 and bone marrow derived stem cells (BMDSC) using H<sub>2</sub>S (AzMC, MeRho-AZ) and PS (SSP4) fluorophores. All MnPs decreased intracellular H<sub>2</sub>S production and increased intracellular PS. H<sub>2</sub>S metabolism and PS production were unaffected by cellular O<sub>2</sub> (5% versus 21% O<sub>2</sub>), H<sub>2</sub>O<sub>2</sub> or ascorbic acid. We observed with confocal microscopy that mitochondria are a major site of H<sub>2</sub>S production in HEK293 cells and that MnPs decrease mitochondrial H<sub>2</sub>S production and increase PS in what appeared to be nucleoli and cytosolic fibrillary elements. This supports a role for MnPs in the metabolism of H<sub>2</sub>S 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. |
topic |
reactive sulfide species ros antioxidants mn porphyrins sod mimetics h<sub>2</sub>s polysulfides |
url |
https://www.mdpi.com/1420-3049/25/4/980 |
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