Nitric oxide (• NO) interactions with biological thiols play crucial, but incompletely determined, roles in vascular signalling and other biological processes. Here, we highlight two recently proposed signalling paradigms: (1) the formation of a vasodilating labile nitrosyl ferrous haem (NO-ferrohaem) facilitated by thiols via thiyl radical generation and (2) polysulfides/persulfides and their interaction with • NO. We also describe the specific (bio)chemical routes in which • NO and thiols react to form S-nitrosothiols, a broad class of small molecules, and protein post-translational modifications that can influence protein function through catalytic site or allosteric structural changes. S-Nitrosothiol formation depends upon cellular conditions, but critically, an appropriate oxidant for either the thiol (yielding a thiyl radical) or • NO (yielding a nitrosonium [NO+ ]-donating species) is required. We examine the roles of these collective • NO/thiol species in vascular signalling and their cardiovascular therapeutic potential.
Keywords: NO-ferrohaem; S-nitrosothiols; labile haem; nitric oxide (•NO); nitrosation; nitrosylation; persulfides; polysulfides; thiyl radicals; vascular and cardiovascular disease.
© 2023 British Pharmacological Society.