NO-releasing NSAIDs are caspase inhibitors.
Nitrosation of thiol-containing proteins is a mechanism for cell regulation. Nitric-oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are chemical entities obtained by adding a nitroxybutyl moiety to a conventional NSAID. NO-NSAIDs inhibit inflammation via cyclo-oxygenase (COX)-dependent and -independent effects. Similarly to endogenous NO, NO-NSAIDs are potent inhibitors of T helper1 (Th1) type cytokines. This effect is largely owing to post-translational nitrosation and therefore inactivation of cysteine proteases, such as the interleukin (IL)-1beta converting enzyme (ICE/caspase-1) involved in pro-cytokine processing.
Fiorucci
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Clinica di Gastroenterologia ed Endoscopia Digestiva, Dipartimento di Medicina Clinica e Sperimentale, Universitá di Perugia, 06100 Perugia, Italy. fiorucci@unipg.it
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000145:classification / Q000494:pharmacology*; D001241:Aspirin / Q000031:analogs & derivatives / Q000494:pharmacology; D061945:Caspase Inhibitors; D016207:Cytokines / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D018417:Th1 Cells
D000894:Anti-Inflammatory Agents, Non-Steroidal; D061945:Caspase Inhibitors; D016207:Cytokines; D009589:Nitrogen Oxides; D009569:Nitric Oxide; C102148:nitroaspirin; C039900:nitroxyl; D001241:Aspirin