International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3567 - 3567
Опубликована: Апрель 10, 2025
The discovery of carbon monoxide releasing molecules (CORMs) was one the most impactful innovations in biochemistry, affecting multiple disciplines for past few decades. Sixteen years ago, a ruthenium dimer-containing CORM, CORM-2, enhanced coagulation and diminished fibrinolysis human plasma by modulation fibrinogen, plasmin, α2-antiplasmin via CO binding to putative heme groups attached these proteins. This finding linked exposure settings involving oxygenase-1 upregulation during inflammation or environmental thromboembolic disease hundreds subsequent manuscripts. However, CO-independent effects CORM-2 radical (Ru•) formed release found be responsible many other works. Using novel approach with plasmatic kinetic methods, Ru• posited bind critical histidines amino acids modulate function, excess histidine quench CORM-2-mediated effects. paradigm addition would definitively address if Thus, coagulation/fibrinolytic data were assessed thrombelastography ±CORM-2, ±histidine added. Histidine nearly completely abrogated hypercoagulation concentration-dependent fashion; further, also eliminated all on fibrinolysis. In conclusion, formation, not release, is true molecular mechanism modulating
Язык: Английский