Evidence that the degree of band 3 phosphorylation modulates human erythrocytes nitric oxide efflux--in vitro model of hyperfibrinogenemia.
Recent evidence has shown that plasma fibrinogen, a major cardiovascular risk factor, interacts with the erythrocyte membrane and acts to influence blood flow via erythrocyte nitric oxide (NO) modulation. In the present pioneer in-vitro study, whole blood samples were harvested from healthy subjects and aliquots were incubated in the absence (control aliquots) and presence of fibrinogen at different degrees of band 3 phosphorylation, and the levels of NO, nitrite, nitrate and S-nitroglutathione (GSNO) were determined. Hyperfibrinogenemia interferes with erythrocyte NO mobilization without changing its efflux in a way that seems to be dependent of the degree of band 3 phosphorylation. In presence of higher fibrinogen concentrations the NO efflux is reinforced when band 3 is phosphorylated (p < 0.001). Higher levels of nitrite, nitrate and GSNO were documented (p < 0.05). However, the mechanisms by which fibrinogen signalling modulates erythrocyte function remain to be clarified and are currently under study. These conditions may be considered an approach to be followed in blood storage for transfusions.
University of Lisbon Medical School, Santa Maria Hospital, Lisbon, Portugal. jpedro.gla@gmail.com
J P Lopes
JP
de Almeida
T
T
Freitas-Santos
C
C
Saldanha
D001457:Anion Exchange Protein 1, Erythrocyte / Q000737:chemistry / Q000502:physiology*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D004058:Diffusion; D004151:Dipeptides / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005340:Fibrinogen / Q000032:analysis / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D019833:Genistein / Q000031:analogs & derivatives; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood*; D009573:Nitrites / Q000097:blood; D009574:Nitro Compounds / Q000494:pharmacology; D009994:Osmolar Concentration; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D000072377:Syk Kinase
D001457:Anion Exchange Protein 1, Erythrocyte; D004151:Dipeptides; D005419:Flavonoids; D047908:Intracellular Signaling Peptides and Proteins; D009566:Nitrates; D009573:Nitrites; D009574:Nitro Compounds; D047428:Protein Kinase Inhibitors; C116027:S-nitroglutathione; C067397:4'-amino-6-hydroxyflavone; C071482:calpeptin; D009569:Nitric Oxide; D005340:Fibrinogen; D019833:Genistein; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D005978:Glutathione