Weak platelet agonists and U46619 induce apoptosis-like events in platelets, in the absence of phosphatidylserine exposure.
Platelets express apoptotic markers during storage, while aging and after stimulation with strong agonists thrombin and collagen. It is unknown if the weak agonists ADP and epinephrine or U46619, a thromboxane analog, induce the expression of apoptotic markers in platelets. To answer this question, we measured phosphatidylserine exposure, gelsolin cleavage and decrease in membrane mitochondrial potential after stimulation with these agonists. No phosphatidylserine exposure was evident, however, gelsolin cleavage and a platelet population with a decreased membrane mitochondrial potential appeared, suggesting that in platelets selective agonists can induce apoptosis in the absence of phosphatidylserine exposure. Interestingly, costimulation by thrombin plus collagen together with each of the other agonists increased the phosphatidylserine exposure induced by strong agonists. These findings may be of importance in platelet activation and apoptosis under pathophysiological conditions where multiple effectors are involved.
Tonon
Giovanni
G
American Red Cross, Jerome H Holland Laboratories, Rockville, MD 20855, USA. tonong@mail.nih.gov
Luo
Xunyi
X
Greco
Nicholas J
NJ
Chen
Weidong
W
Shi
Yufang
Y
Jamieson
Graham A
GA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000244:Adenosine Diphosphate / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology*; D001792:Blood Platelets / Q000187:drug effects*; D003094:Collagen / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D018260:Gelsolin / Q000096:biosynthesis; D006801:Humans; D015151:Immunoblotting; D010718:Phosphatidylserines / Q000096:biosynthesis; D013917:Thrombin / Q000494:pharmacology
D018260:Gelsolin; D010718:Phosphatidylserines; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen; D013917:Thrombin; D004837:Epinephrine