S-Transnitrosylation of albumin in human plasma and blood in vitro and in vivo in the rat.
S-Nitrosoalbumin (SNOALB) is the most abundant physiological circulating nitric oxide (NO) carrier regulating NO-dependent biological actions in humans. The mechanisms of its formation and biological actions are still incompletely understood. Nitrosation by authentic NO and S-transnitrosylation of the single sulfhydryl group located at Cys-34 of human albumin by the physiological S-nitroso compounds S-nitrosocysteine (SNOC) and S-nitrosoglutathione (GSNO) are two possible mechanisms. On a quantitative basis, we investigated by gas chromatography-mass spectrometry the contribution of these two mechanisms to SNOALB formation in human plasma and blood in vitro. GSNO and SNOC (0-100 microM) rapidly and efficiently (recovery=35%) S-transnitrosylated albumin to form SNOALB. NO (100 microM) S-nitrosated albumin to SNOALB at a considerably lower extent (recovery=5%). The putative NO-donating drugs glyceryl trinitrate and sodium nitroprusside (each 100 microM) failed completely in S-nitrosating albumin. Bubbling NO into human plasma and blood resulted in formation of SNOALB that inhibited ADP-induced platelet aggregation. Infusion of GS(15)NO in the rat resulted in formation of S(15)NOALB, [(15)N]nitrate and [(15)N]nitrite. Our results suggest that S-transnitrosylation of albumin by SNOC and GSNO could be a more favored mechanism for the formation of SNOALB in the circulation in vivo than S-nitrosation of albumin by NO itself.
Tsikas
D
D
Institute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625, Hannover, Germany.
Sandmann
J
J
Luessen
P
P
Savva
A
A
Rossa
S
S
Stichtenoth
D O
DO
Frölich
J C
JC
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D026422:S-Nitrosoglutathione; D026403:S-Nitrosothiols; D012709:Serum Albumin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000096:biosynthesis* / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism
D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; C091665:S-nitrosoalbumin; D012709:Serum Albumin; D013438:Sulfhydryl Compounds; D009599:Nitroprusside; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D000244:Adenosine Diphosphate; C021315:S-nitrosocysteine; D005996:Nitroglycerin; D005978:Glutathione; D003545:Cysteine