Antioxidative and anti-inflammatory actions of reactive cysteine persulfides

Abstract

Cysteine persulfide (CysSSH) and polysulfides (CysS[S] _n H, n>1) are cysteine derivatives having sulfane sulfur atoms bound to cysteine thiol. Recent advances in the development of analytical methods for detection and quantification of persulfides and polysulfides have revealed the biological presence, in both prokaryotes and eukaryotes, of persulfide/polysulfide in diverse forms such as CysSSH, glutathione persulfide and protein persulfides. Accumulating evidence has suggested that persulfide/polysulfide species may involve in a variety of biological events such as biosyntheses of sulfur-containing molecules, tRNA modification, regulation of redox-dependent signal transduction, mitochondrial energy metabolism via sulfur respiration, cytoprotection from oxidative stress via their antioxidant activities, and anti-inflammation against Toll-like receptor-mediated inflammatory responses. Development of chemical sulfur donors may facilitate further understanding of physiological and pathophysiological roles of persulfide/polysulfide species, including regulatory roles of these species in immune responses.

Keywords: anti-inflammatory effect; antioxidant; electrophile; persulfide; reactive sulfur species.

Fig. 1

Chemical structures of representative endogenous persulfide species.

Fig. 2

Chemical structures of NAC polysulfide (NAC-S2) and related compound. oxNAC is a control reagent having no polysulfide donating capability. NAC-S2 is a polysulfide donor that transfers their sulfane sulfur (S⁰) to acceptor thiols.

Fig. 3

Suppression of immune responses by NAC polysulfide. NAC polysulfide that penetrates plasma membrane increases intracellular reactive sulfur species by donating its sulfur to acceptor thiols. In inflammatory cells such as macrophages treated with NAC polysulfide, TLR ligand stimulation is remarkably suppressed.