Manganese Porphyrin-Based SOD Mimetics Produce Polysulfides from Hydrogen Sulfide
by
Kenneth R. Olson 1,2,*
, Yan Gao 1, Faihaan Arif 1, Shivali Patel 1, Xiaotong Yuan 3, Varun Mannam 3, Scott Howard 3, Ines Batinic-Haberle 4, Jon Fukuto 5, Magdalena Minnion 6,7, Martin Feelisch 6,7 and Karl D. Straub 8,9
Kenneth R. Olson 1,2,*, Yan Gao 1, Faihaan Arif 1, Shivali Patel 1, Xiaotong Yuan 3, Varun Mannam 3, Scott Howard 3, Ines Batinic-Haberle 4, Jon Fukuto 5, Magdalena Minnion 6,7, Martin Feelisch 6,7 and Karl D. Straub 8,9
1
Indiana University School of Medicine—South Bend, South Bend, IN 46617, USA
2
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA
3
Department of Electrical Engineering, University of Notre Dame, Notre Dame, IN 46556, USA
4
Department of Radiation Oncology, School of Medicine, Duke University, Durham, NC 27710, USA
5
Department of Chemistry, Sonoma State University, Rohnert Park, CA 94928, USA
6
NIHR Southampton Biomedical Research Center, University of Southampton, Southampton, General Hospital, Southampton SO16 6YD, UK
7
Clinical & Experimental Sciences, Faculty of Medicine, Southampton General Hospital and Institute for Life Sciences, University of Southampton, Southampton SO16 6YD, UK
8
Central Arkansas Veteran’s Healthcare System, Little Rock, AR 72205, USA
9
Departments of Medicine and Biochemistry, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA
*
Author to whom correspondence should be addressed.
Antioxidants 2019, 8(12), 639; https://doi.org/10.3390/antiox8120639
Received: 22 November 2019 / Revised: 4 December 2019 / Accepted: 6 December 2019 / Published: 12 December 2019
(This article belongs to the Special Issue Redox Regulation of Cell Signalling)
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.
View Full-Text
Keywords:
H2S; reactive sulfur species; reactive oxygen species; Mn porphyrins; BMX-001; antioxidants
▼
Show Figures
Figure 1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
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. Manganese Porphyrin-Based SOD Mimetics Produce Polysulfides from Hydrogen Sulfide. Antioxidants 2019, 8, 639.
Show more citation formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.
