Abstract
Hydrogen sulfide (H(2)S) and polysulfides including H(2)S(n) (n = 2 or more) regulate neuronal activity, vascular tone, oxytosis/ferroptosis, oxygen sensing, cancer growth and senescence. Cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST) produce H(2)S. Polysulfides are also produced by various enzymes including 3MST. In addition, transient receptor potential ankyrin 1 (TRPA1) channel-an important polysulfide target-modulates sulfur metabolism (including cysteine, H(2)S and polysulfides) and also affects the neurotransmitter GABA. Polysulfides persulfidate the cysteine residues of the target proteins, causing conformational changes that alter their activity. By contrast, H(2)S persulfidates oxidized cysteine residues (e.g., S-nitrosylated- and S-sulfinated) in its targets. H(2)S/polysulfides protect neurons from oxidative stress and thereby protect cells against various forms of cell death including oxytosis and ferroptosis. A deviation from normal H(2)S and polysulfides levels has been suggested to play a role in the pathophysiology of various neuronal- and psychiatric diseases.