Thrombin-induced caspases 3 and 9 translocation to the cytoskeleton is independent of changes in cytosolic calcium in human platelets.
Apoptosis has been shown to be associated with changes in cytosolic free calcium concentration ([Ca(2+)](c)). Here we show that the agonist thrombin induces activation of caspases 9 and 3 and translocation of the caspase active forms and procaspases to the cytoskeleton in human platelets. Dimethyl-BAPTA loading did not affect thrombin-induced caspase 9 and 3 activation or translocation suggesting that these responses are independent of increases in [Ca(2+)](c). Treatment with thapsigargin plus ionomycin, to induce extensive Ca(2+) store depletion and subsequent increase in [Ca(2+)](c), stimulates caspase activation although it was unable to induce caspase translocation to the cytoskeleton. Similar results were observed in cells loaded with dimethyl-BAPTA, suggesting that activation of caspases 9 and 3 by thapsigargin plus ionomycin does not require rises in [Ca(2+)](c). These findings suggest that thrombin-induced caspase 9 and 3 activation and translocation are independent on rises in [Ca(2+)](c) but might require store depletion in human platelets.
Amor
Nidhal B
NB
Unité de Recherche de Biochimie, Institut Supérieur de Biotechnologie, 5019-Monastir, Tunisia.
Pariente
Juan A
JA
Salido
Ginés M
GM
Rosado
Juan A
JA
Bartegi
Aghleb
A
D001792:Blood Platelets / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D021381:Protein Transport / Q000187:drug effects; D019284:Thapsigargin / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism* / Q000494:pharmacology
D002614:Chelating Agents; D004791:Enzyme Inhibitors; D004533:Egtazic Acid; D019284:Thapsigargin; D013917:Thrombin; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium