Interference of activated factor VII in apoptosis of erytholeukemic K562 cells.
Coagulation factor VIIa (FVIIa) is a key protease initiating the coagulation cascade in the presence of its receptor, tissue factor (TF). FVIIa elicits several cellular responses, probably involving other receptors(s) than TF. This study investigates the implication of recombinant FVIIa on the apoptosis of K562 erythroleukemia cells. These cells undergo apoptosis when induced to differentiate towards the erythroid lineage by hemin. They do not express TF, but can be transfected to do so. FVIIa treatment significantly reduced the degree of hemin-induced apoptosis in K562 cells, but not in TF+ derived transfectants. Induction of apoptosis by hemin also elicited decrease in intracellular Ca2+ concentration ([Ca2+]i), but FVIIa restored this [Ca2+]i close to that of non-treated cells. These results suggest that FVIIa acts via a TF-independent pathway to counteract apoptosis by a mechanism involving its Gla domain and linked to the maintenance of Ca2+ homeostasis in K562 cells.
Kunzelman
Corinne
C
Unité 143 INSERM, hôpital de Bicêtre, 78, rue du Général-Leclerc, 94270 Le Kremlin-Bicêtre, France.
Toti
Florence
F
Freyssinet
Jean-Marie
JM
Meyer
Dominique
D
D017209:Apoptosis / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000235:genetics; D004171:Diploidy; D015942:Factor VIIa / Q000494:pharmacology*; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D011516:Prothrombin / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013925:Thromboplastin / Q000187:drug effects / Q000502:physiology; D014162:Transfection
D004273:DNA, Neoplasm; D011994:Recombinant Proteins; D006427:Hemin; D011516:Prothrombin; D013925:Thromboplastin; D015942:Factor VIIa