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

Chem Res Toxicol. 2019 Mar 18;32(3):447-455. doi: 10.1021/acs.chemrestox.8b00340. Epub 2019 Feb 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Cysteine / chemistry
  • Cysteine / metabolism*
  • Cysteine / toxicity*
  • Humans
  • Mice
  • Molecular Structure
  • Sulfides / chemistry
  • Sulfides / metabolism*
  • Sulfides / toxicity*
  • Tetrazolium Salts / pharmacology

Substances

  • 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H tetrazolium monosodium salt
  • Sulfides
  • Tetrazolium Salts
  • polysulfide
  • Cysteine