Cooperative Interactions Between NO and H2S: Chemistry, Biology, Physiology, Pathophysiology

摘要: Abstract The mutual interaction of sulfide and NO (also known as the “NO/H2S cross-talk”) has both chemical biological foundations. With respect to aspects, formation an intermediary nitrosothiol was proposed after reaction H2S, which initially attributed highly reactive short-lived HSNO. Subsequent studies focusing on reactivity aqueous solutions with nitrosothiols, peroxynitrite, donors such sodium nitroprusside revealed that kinetics mechanisms are complex only partially understood. Recent work in this area resulted rediscovery a forgotten chemistry S-N hybrid molecules, class compounds characterized more than half century ago. Other lines investigations or nitrosothiols under biologically relevant conditions leads three different classes intermediates including ONSS− (perthionitrite, nitrosopersulfide), S x 2 − (polysulfides chain lengths), ON ( ) O 3 (the NONOate SULFI/NO); their generation contributes scavenging, storage transport, redox conversion HNO, sulfane sulfur signaling. These reactions be fundamental significance for signaling by modulating its bioactivity via new entities properties distinct from those NO. release H2S various stable semistable “pools” can contribute responses H2S. one level between relates convergence AKT PI3K signaling, part due activation inhibition phosphatase tensin homolog (PTEN) processes lead increased intracellular PIP3 levels, which, turn, synthase combination phosphorylation dephosphorylation critical tyrosine residues. In addition, converge checkpoints guanylate cyclase/cGMP/protein kinase G; reduce cyclase, thereby preventing oxidative inactivation; inhibit phosphodiesterases, prolonging half-life cGMP, H2S-derived polysulfides activate protein G. Moreover, directly interact NOS, resulting sulfhydrative stabilization physiological, dimeric state. many experimental models, protective vascular effects diminished absent absence functional eNOS, further underlining importance cooperative NO/H2S interactions.