Differential erythropoietin action upon cells induced to eryptosis by different agents.
Eryptosis is a process by which mature erythrocytes can undergo self-destruction sharing several features with apoptosis. Premature programmed erythrocyte death may be induced by different agents. In this study, we compared mechanisms involved in two eryptotic models (oxidative stress and cell calcium overload) so as to distinguish whether they share signaling pathways and could be prevented by erythropoietin (Epo). Phosphatidylserine (PS) translocation and increased calcium content were common signs in erythrocytes exposed to sodium nitrite plus hydrogen peroxide or calcium ionophore A23187 (CaI), while increased ROS and decreased GSH levels were detected in the oxidative model. Protein kinase activation seemed to be an outstanding feature in eryptosis induced by oxidative stress, whereas phosphatase activation was favored in the CaI model. Cell morphology and membrane protein modifications were also differential signs between both models. Epo was able to prevent cell oxidative imbalance, thus blunting PS translocation. However, the hormone favored intracellular calcium influx which could be the reason why it could not completely counteract the induction of eryptosis. Instead, Epo was unable to inhibit PS externalization in the CaI model. The different mechanisms involved in the eryptotic models may explain the differential action of Epo upon erythrocytes induced to eryptosis by different agents.
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Buenos Aires, Argentina.
Daiana M
DM
Vota
Romina E
RE
Maltaneri
Shirley D
SD
Wenker
Alcira B
AB
Nesse
Daniela C
DC
Vittori
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012977:Sodium Nitrite / Q000494:pharmacology
D007476:Ionophores; D016877:Oxidants; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D004921:Erythropoietin; D000001:Calcimycin; D006861:Hydrogen Peroxide; D012977:Sodium Nitrite; D002118:Calcium