Platelet Senescence and Phosphatidylserine Exposure

Overview

Journal Transfusion

Specialty Hematology

Date 2010 May 12

PMID 20456701

Citations 17

Authors

Swapan Kumar Dasgupta

Eduardo Rios Argaiz

Jose Emmanel Chedid Mercado

Hector Omar Elizondo Maul

Jorge Garza

Ana Bety Enriquez

Hanan Abdel-Monem

Anthony Prakasam

Michael Andreeff

Perumal Thiagarajan

Affiliations

Soon will be listed here.

Abstract

Background: The exposure of phosphatidylserine occurs during platelet (PLT) activation and during in vitro storage. Phosphatidylserine exposure also occurs during apoptosis after the release of mitochondrial cytochrome c. We have examined the role of cytochrome c release, mitochondrial membrane potential (ΔΨm), and cyclophilin D (CypD) in phosphatidylserine exposure due to activation and storage.

Study Design And Methods: The exposure of phosphatidylserine and the loss of ΔΨm were determined in a flow cytometer using fluorescein isothiocyanate-lactadherin and JC-1, a lipophilic cationic reporter dye. The role of CypD was determined with cyclosporin A and CypD-deficient murine PLTs. Cytochrome c-induced caspase-3 and Rho-associated kinase I (ROCK1) activation were determined by immunoblotting and using their inhibitors.

Results: Collagen- and thrombin-induced exposure of phosphatidylserine was accompanied by a decrease in ΔΨm. Cyclosporin A inhibited the phosphatidylserine exposure and the loss of ΔΨm. CypD(-/-) mice had decreased loss of ΔΨm and impaired phosphatidylserine exposure. Collagen and thrombin did not induce the release of cytochrome c nor the activation of caspase-3 and ROCK1. In contrast, in PLTs stored for more than 5 days, the phosphatidylserine exposure was associated with cytochrome c-induced caspase-3 and ROCK1 activation. ABT737, a BH3 mimetic that induces mitochondrial pathway of apoptosis, induced cytochrome c release and activation of caspase-3 and ROCK1 and phosphatidylserine exposure independent of CypD.

Conclusion: These results show that in stored PLTs cytochrome c release and the subsequent activation of caspase-3 and ROCK1 mediate phosphatidylserine exposure and it is distinct from activation-induced phosphatidylserine exposure.

Citing Articles

The platelet storage lesion, what are we working for?.

Liu C, Su Y, Guo W, Ma X, Qiao R J Clin Lab Anal. 2023; 38(1-2):e24994.

PMID: 38069592 PMC: 10829691. DOI: 10.1002/jcla.24994.

Gamma irradiation induces a pro-apoptotic state in longer stored platelets, without progressing to an overt apoptosis by day 7 of storage.

Hosseini E, Nodeh F, Ghasemzadeh M Apoptosis. 2023; 28(7-8):1141-1153.

PMID: 37127837 DOI: 10.1007/s10495-023-01841-5.

What can we learn from senescent platelets, their transcriptomes and proteomes?.

Allan H, Vadgama A, Armstrong P, Warner T Platelets. 2023; 34(1):2200838.

PMID: 37070955 PMC: 10124551. DOI: 10.1080/09537104.2023.2200838.

Reduced platelet glycoprotein Ibα shedding accelerates thrombopoiesis and COX-1 recovery: implications for aspirin dosing regimen.

Simeone P, Liani R, Tripaldi R, Ciotti S, Recchiuti A, Abbonante V Haematologica. 2022; 108(4):1141-1157.

PMID: 36546455 PMC: 10071111. DOI: 10.3324/haematol.2022.281006.

In Vitro Comparative Study of Platelets Treated with Two Pathogen-Inactivation Methods to Extend Shelf Life to 7 Days.

Malvaux N, Defraigne F, Bartziali S, Bellora C, Mommaerts K, Betsou F Pathogens. 2022; 11(3).

PMID: 35335667 PMC: 8949436. DOI: 10.3390/pathogens11030343.

References

Morison I, Cramer Borde E, Cheesman E, Cheong P, Holyoake A, Fichelson S . A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia. Nat Genet. 2008; 40(4):387-9. DOI: 10.1038/ng.103. View

Thiagarajan P, Tait J . Collagen-induced exposure of anionic phospholipid in platelets and platelet-derived microparticles. J Biol Chem. 1991; 266(36):24302-7. View

Graier W, Frieden M, Malli R . Mitochondria and Ca(2+) signaling: old guests, new functions. Pflugers Arch. 2007; 455(3):375-96. PMC: 4864527. DOI: 10.1007/s00424-007-0296-1. View

Remenyi G, Szasz R, Friese P, Dale G . Role of mitochondrial permeability transition pore in coated-platelet formation. Arterioscler Thromb Vasc Biol. 2004; 25(2):467-71. DOI: 10.1161/01.ATV.0000152726.49229.bf. View

Shapira S, Friedman Z, Shapiro H, Presseizen K, Radnay J, Ellis M . The effect of storage on the expression of platelet membrane phosphatidylserine and the subsequent impacton the coagulant function of stored platelets. Transfusion. 2000; 40(10):1257-63. DOI: 10.1046/j.1537-2995.2000.40101257.x. View

Perrotta P, Perrotta C, Snyder E . Apoptotic activity in stored human platelets. Transfusion. 2003; 43(4):526-35. DOI: 10.1046/j.1537-2995.2003.00349.x. View

Ravichandran K, Lorenz U . Engulfment of apoptotic cells: signals for a good meal. Nat Rev Immunol. 2007; 7(12):964-74. DOI: 10.1038/nri2214. View

Leung A, Halestrap A . Recent progress in elucidating the molecular mechanism of the mitochondrial permeability transition pore. Biochim Biophys Acta. 2008; 1777(7-8):946-52. DOI: 10.1016/j.bbabio.2008.03.009. View

Jobe S, Wilson K, Leo L, Raimondi A, Molkentin J, Lentz S . Critical role for the mitochondrial permeability transition pore and cyclophilin D in platelet activation and thrombosis. Blood. 2007; 111(3):1257-65. PMC: 2214770. DOI: 10.1182/blood-2007-05-092684. View

10.

Ahmad S, Walsh P . Components and assembly of the factor X activating complex. Semin Thromb Hemost. 1992; 18(3):311-23. DOI: 10.1055/s-2007-1002570. View

11.

Murphy S . Radiolabeling of PLTs to assess viability: a proposal for a standard. Transfusion. 2003; 44(1):131-3. DOI: 10.1111/j.0041-1132.2003.00607.x. View

12.

Bertino A, Qi X, Li J, Xia Y, Kuter D . Apoptotic markers are increased in platelets stored at 37 degrees C. Transfusion. 2003; 43(7):857-66. DOI: 10.1046/j.1537-2995.2003.t01-4-00431.x. View

13.

Riento K, Ridley A . Rocks: multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol. 2003; 4(6):446-56. DOI: 10.1038/nrm1128. View

14.

Oltersdorf T, Elmore S, Shoemaker A, Armstrong R, Augeri D, Belli B . An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005; 435(7042):677-81. DOI: 10.1038/nature03579. View

15.

Thiagarajan P, Tait J . Binding of annexin V/placental anticoagulant protein I to platelets. Evidence for phosphatidylserine exposure in the procoagulant response of activated platelets. J Biol Chem. 1990; 265(29):17420-3. View

16.

Cauwenberghs S, van Pampus E, Curvers J, Akkerman J, Heemskerk J . Hemostatic and signaling functions of transfused platelets. Transfus Med Rev. 2007; 21(4):287-94. DOI: 10.1016/j.tmrv.2007.05.004. View

17.

Rand M, Wang H, Bang K, Poon K, Packham M, Freedman J . Procoagulant surface exposure and apoptosis in rabbit platelets: association with shortened survival and steady-state senescence. J Thromb Haemost. 2004; 2(4):651-9. DOI: 10.1111/j.1538-7836.2004.00670.x. View

18.

Bode A, Miller D . Analysis of platelet factor 3 in platelet concentrates stored for transfusion. Vox Sang. 1986; 51(4):299-305. DOI: 10.1111/j.1423-0410.1986.tb01972.x. View

19.

Dasgupta S, Guchhait P, Thiagarajan P . Lactadherin binding and phosphatidylserine expression on cell surface-comparison with annexin A5. Transl Res. 2006; 148(1):19-25. DOI: 10.1016/j.lab.2006.03.006. View

20.

Cragg M, Harris C, Strasser A, Scott C . Unleashing the power of inhibitors of oncogenic kinases through BH3 mimetics. Nat Rev Cancer. 2009; 9(5):321-6. DOI: 10.1038/nrc2615. View