The effect of reagents mimicking oxidative stress on fibrinogen function.
Fibrinogen is one of the plasma proteins most susceptible to oxidative modification. It has been suggested that modification of fibrinogen may cause thrombotic/bleeding complications associated with many pathophysiological states of organism. We exposed fibrinogen molecules to three different modification reagents-malondialdehyde, sodium hypochlorite, and peroxynitrite-that are presented to various degrees in different stages of oxidative stress. We studied the changes in fibrin network formation and platelet interactions with modified fibrinogens under flow conditions. The fastest modification of fibrinogen was caused by hypochlorite. Fibers from fibrinogen modified with either reagent were thinner in comparison with control fibers. We found that platelet dynamic adhesion was significantly lower on fibrinogen modified with malondialdehyde and significantly higher on fibrinogen modified either with hypochlorite or peroxynitrite reflecting different prothrombotic/antithrombotic properties of oxidatively modified fibrinogens. It seems that, in the complex reactions ongoing in living organisms at conditions of oxidation stress, hypochlorite modifies proteins (e.g., fibrinogen) faster and more preferentially than malondialdehyde. It suggests that the prothrombotic effects of prior fibrinogen modifications may outweigh the antithrombotic effect of malondialdehyde-modified fibrinogen in real living systems.
Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 00 Prague 2, Czech Republic.
Jana
J
Štikarová
Roman
R
Kotlín
Tomáš
T
Riedel
Jiří
J
Suttnar
Kristýna
K
Pimková
Leona
L
Chrastinová
Jan E
JE
Dyr
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D005340:Fibrinogen / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents / Q000737:chemistry / Q000494:pharmacology; D008315:Malondialdehyde / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D030421:Peroxynitrous Acid / Q000737:chemistry*; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology; D012973:Sodium Hypochlorite / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D030421:Peroxynitrous Acid; D008315:Malondialdehyde; D005340:Fibrinogen; D012973:Sodium Hypochlorite