Influence of glutathione and its derivatives on fibrin polymerization.
A complex relationship exists between reduced, oxidized, and nitrosated glutathione (GSH, GSSG, and GSNO, respectively). Although previous studies have demonstrated S-nitrosoglutathione (GSNO) has potent antiplatelet efficacy, little work has examined the role of GSNO and related species on subsequent aspects of coagulation (e.g., fibrin polymerization). Herein, the effects of GSH, GSSG, and GSNO on the entire process of fibrin polymerization are described. Relative to normal fibrinogen, the addition of GSH, GSSG, or GSNO leads to prolonged lag times, slower rates of protofibril lateral aggregation and the formation of clots with lower final turbidities. Dose-dependent studies indicate the influence of GSH on fibrin formation is a function of both GSH and fibrinogen concentration. Studies with Aalpha251 recombinant fibrinogen (lacking alphaC regions) showed GSH had no influence on its polymerization, suggesting the glutathione species interact within the alphaC region of fibrinogen.
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Carri B
CB
Geer
Nathan A
NA
Stasko
Ioana A
IA
Rus
Susan T
ST
Lord
Mark H
MH
Schoenfisch
D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000096:biosynthesis*; D005978:Glutathione / Q000494:pharmacology*; D019803:Glutathione Disulfide / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D009391:Nephelometry and Turbidimetry; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism
D026422:S-Nitrosoglutathione; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin; D005978:Glutathione; D019803:Glutathione Disulfide