Platelet aging in vivo is associated with activation of apoptotic pathways: Studies in a model of suppressed thrombopoiesis in dogs

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dc.contributor.authorPereira, J
dc.contributor.authorSoto, M
dc.contributor.authorPalomo, I
dc.contributor.authorOcqueteau, M
dc.contributor.authorCoetzee, LM
dc.contributor.authorAstudillo, S
dc.contributor.authorAranda, E
dc.contributor.authorMezzano, D
dc.date.accessioned2024-01-10T12:41:31Z
dc.date.available2024-01-10T12:41:31Z
dc.date.issued2002
dc.description.abstractThe mechanism(s) involved in the clearance of senescent platelets are largely unknown. We have recently demonstrated that platelet aging in vivo is associated with loss of membrane phospholipid asymmetry, a universal phenomenon in cells undergoing apoptosis. Thus, We postulated that senescent platelets may exhibit programmed cell death changes, which may trigger their removal from circulation. Since platelets contain the apoptosis machinery as well as mitochondria, a key organelle in the regulation of apoptosis, we studied the appearance of apoptotic-like changes during platelet aging in vivo. To investigate this, we assessed changes in mitochondrial membrane potential in circulating canine platelets during decline in platelet Count after suppression of thrombopoiesis by estradiol injection. a validated model to obtain circulating platelets of increasing mean ace. Phosphatidyl-serine (PS) exposure was determined by flow cytometry by binding of FITC-labeled annexin V. Mitochondrial Deltapsi was studied with the cationic lipophilic dye DIOC6 (3) and the J-aggregate-forming cation JC-1 and analysis by flow cytometry. The proportion of platelets with exposed PS rose significantly with age, from 2.88% before to 6.7%. 8 days after estradiol injection. By flow, cytometry it was demonstrated a significant decreased in DIOC6 (3) fluorescence (median fluorescence intensity 791 98 vs 567 1021 day 0 vs day 8 post injection of estradiol, respectively n:11; p<0.01), consistent with mitochondrial &UDelta;&psi; collapse. JC-1 has the unique property of forming J-aggregates tinder high mitochondrial &UDelta;&psi; (red fluorescence, FL2) whereas the monomeric form fluoresces in green (FL1). Aged platelets in vivo, loaded with JC-1, exhibited a significant increase in FL1/FL2 ratio (2.5&PLUSMN;1.7 vs 4.7&PLUSMN;1.6, day 0 vs day 8 post injection of estradiol, respectively n:13; p<0.05). confirming the mitochondrial Deltapsi alteration.
dc.description.abstractThe results show that platelet aging in vivo is associated with a decrease in mitochondrial Deltapsi and PS exposure. In conclusion. our data provide for the first time, evidence that platelet senescence is associated with changes characteristics of apoptosis, which may promote their removal from circulation.
dc.fechaingreso.objetodigital2024-05-14
dc.format.extent5 páginas
dc.fuente.origenWOS
dc.identifier.issn0340-6245
dc.identifier.pubmedidMEDLINE:12038796
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/77424
dc.identifier.wosidWOS:000175682100022
dc.information.autorucMedicina;Mezzano D;S/I;99455
dc.information.autorucMedicina;Pereira J;S/I;99371
dc.issue.numero5
dc.language.isoen
dc.nota.accesoSin adjunto
dc.pagina.final909
dc.pagina.inicio905
dc.publisherSCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
dc.revistaTHROMBOSIS AND HAEMOSTASIS
dc.rightsregistro bibliográfico
dc.subjectplatelet aging
dc.subjectapoptosis
dc.subjectmitochondria
dc.subjectplatelet removal
dc.subjectMEMBRANE PHOSPHOLIPID ASYMMETRY
dc.subjectCELL-DEATH
dc.subjectLYMPHOCYTE APOPTOSIS
dc.subjectBLOOD-CELLS
dc.subjectMITOCHONDRIAL
dc.subjectPHOSPHATIDYLSERINE
dc.subjectEXPOSURE
dc.subjectJC-1
dc.subjectCLEARANCE
dc.subjectRECEPTOR
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePlatelet aging in vivo is associated with activation of apoptotic pathways: Studies in a model of suppressed thrombopoiesis in dogs
dc.typeartículo
dc.volumen87
sipa.codpersvinculados99455
sipa.codpersvinculados99371
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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