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The Uptake and Release of Polysulfur Cysteine Species by Cells: Physiological and Toxicological Implications

  • Joseph Lin*
    Joseph Lin
    Department of Biology, Sonoma State University, Rohnert Park, California 94928, United States
    *E-mail: [email protected]
    More by Joseph Lin
  • Masahiro Akiyama
    Masahiro Akiyama
    Environmental Biology Section, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
  • Iris Bica
    Iris Bica
    Department of Biology, Sonoma State University, Rohnert Park, California 94928, United States
    More by Iris Bica
  • Faith T. Long
    Faith T. Long
    Department of Biology, Sonoma State University, Rohnert Park, California 94928, United States
  • Catherine F. Henderson
    Catherine F. Henderson
    Department of Biology, Sonoma State University, Rohnert Park, California 94928, United States
  • Robert N. Goddu
    Robert N. Goddu
    Department of Biology, Sonoma State University, Rohnert Park, California 94928, United States
  • Valeria Suarez
    Valeria Suarez
    Department of Chemistry, Sonoma State University, Rohnert Park, California 94928, United States
  • Blaine Baker
    Blaine Baker
    Department of Chemistry, Sonoma State University, Rohnert Park, California 94928, United States
    More by Blaine Baker
  • Tomoaki Ida
    Tomoaki Ida
    Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
    More by Tomoaki Ida
  • Yasuhiro Shinkai
    Yasuhiro Shinkai
    Environmental Biology Section, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
  • Peter Nagy
    Peter Nagy
    Department of Molecular Immunology and Toxicology, National Institute of Oncology, Budapest 1122, Hungary
    More by Peter Nagy
  • Takaaki Akaike
    Takaaki Akaike
    Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
  • Jon M. Fukuto*
    Jon M. Fukuto
    Department of Chemistry, Sonoma State University, Rohnert Park, California 94928, United States
    *E-mail: [email protected]
  • , and 
  • Yoshito Kumagai*
    Yoshito Kumagai
    Environmental Biology Section, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
    *E-mail: [email protected]
Cite this: Chem. Res. Toxicol. 2019, 32, 3, 447–455
Publication Date (Web):January 25, 2019
https://doi.org/10.1021/acs.chemrestox.8b00340
Copyright © 2019 American Chemical Society
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Abstract

Abstract Image

Hydropersulfides and related polysulfides have recently become topics of significant interest due to their physiological prevalence and proposed biological functions. Currently, examination of the effects of hydropersulfide treatment on cells is difficult due to their lack of inherent stability with respect to disproportionation. Herein, it is reported that the treatment of a variety of cell types with cysteine trisulfide (also known as thiocystine; Cys-SSS-Cys), results in an increase in intracellular hydropersulfide levels (e.g., cysteine hydropersulfide; Cys-SSH, and glutathione hydropersulfide; GSSH). Thus, Cys-SSS-Cys represents a possible pharmacological agent for examining the effects of hydropersulfides on cell function/viability. It has also been found that cells with increased intracellular hydropersulfide levels can export Cys-SSH into the extracellular media. Interestingly, the Cys-SSH is the major hydropersulfide exported by cells, although GSSH is the predominant intracellular species. The possible implications of cellular export are discussed.

Cited By


This article is cited by 10 publications.

  1. Nam V. Dao, Francesca Ercole, Lisa M. Kaminskas, Thomas P. Davis, Erica K. Sloan, Michael R. Whittaker, John F. Quinn. Trisulfide-Bearing PEG Brush Polymers Donate Hydrogen Sulfide and Ameliorate Cellular Oxidative Stress. Biomacromolecules 2020, 21 (12) , 5292-5305. https://doi.org/10.1021/acs.biomac.0c01347
  2. Vinayak S. Khodade, Blaze M. Pharoah, Nazareno Paolocci, John P. Toscano. Alkylamine-Substituted Perthiocarbamates: Dual Precursors to Hydropersulfide and Carbonyl Sulfide with Cardioprotective Actions. Journal of the American Chemical Society 2020, 142 (9) , 4309-4316. https://doi.org/10.1021/jacs.9b12180
  3. Catherine F. Henderson, Iris Bica, Faith T. Long, Drew D. Irwin, Christine H. Stull, Blaine W. Baker, Valeria Suarez Vega, Zachary M. Taugher, Eliza D. Fletes, Juliet M. Bartleson, Megan L. Humphrey, Lucía Álvarez, Masahiro Akiyama, Yoshito Kumagai, Jon M. Fukuto, Joseph Lin. Cysteine Trisulfide Protects E. coli from Electrophile-Induced Death through the Generation of Cysteine Hydropersulfide. Chemical Research in Toxicology 2020, 33 (2) , 678-686. https://doi.org/10.1021/acs.chemrestox.9b00494
  4. Kearsley M. Dillon, Holly A. Morrison, Chadwick R. Powell, Ryan J. Carrazzone, Veronica M. Ringel‐Scaia, Ethan W. Winckler, R. McAlister Council‐Troche, Irving C. Allen, John B. Matson. Targeted Delivery of Persulfides to the Gut: Effects on the Microbiome. Angewandte Chemie 2021, 16 https://doi.org/10.1002/ange.202014052
  5. Kearsley M. Dillon, Holly A. Morrison, Chadwick R. Powell, Ryan J. Carrazzone, Veronica M. Ringel‐Scaia, Ethan W. Winckler, R. McAlister Council‐Troche, Irving C. Allen, John B. Matson. Targeted Delivery of Persulfides to the Gut: Effects on the Microbiome. Angewandte Chemie International Edition 2021, 16 https://doi.org/10.1002/anie.202014052
  6. Jon M. Fukuto, Joseph Lin, Vinayak S. Khodade, John P. Toscano. Predicting the Possible Physiological/Biological Utility of the Hydropersulfide Functional Group Based on Its Chemistry: Similarities Between Hydropersulfides and Selenols. Antioxidants & Redox Signaling 2020, 33 (18) , 1295-1307. https://doi.org/10.1089/ars.2020.8079
  7. Kenneth R. Olson, Austin Briggs, Monesh Devireddy, Nicholas A. Iovino, Nicole C. Skora, Jenna Whelan, Brian P. Villa, Xiaotong Yuan, Varun Mannam, Scott Howard, Yan Gao, Magdalena Minnion, Martin Feelisch. Green tea polyphenolic antioxidants oxidize hydrogen sulfide to thiosulfate and polysulfides: A possible new mechanism underpinning their biological action. Redox Biology 2020, 37 , 101731. https://doi.org/10.1016/j.redox.2020.101731
  8. Brenna J.C. Walsh, David P. Giedroc. H2S and reactive sulfur signaling at the host-bacterial pathogen interface. Journal of Biological Chemistry 2020, 295 (38) , 13150-13168. https://doi.org/10.1074/jbc.REV120.011304
  9. Hironori Kanda, Yoshito Kumagai. Redox Signaling and Reactive Sulfur Species to Regulate Electrophilic Stress. YAKUGAKU ZASSHI 2020, 140 (9) , 1119-1128. https://doi.org/10.1248/yakushi.20-00096
  10. Kenneth R. Olson. Are Reactive Sulfur Species the New Reactive Oxygen Species?. Antioxidants & Redox Signaling 2020, https://doi.org/10.1089/ars.2020.8132

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