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Differential Erythropoietin Action upon Cells Induced to Eryptosis by Different Agents

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Abstract

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.

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Abbreviations

PMSF:

Phenylmethylsulfonyl fluoride

SBTI:

Soybean trypsin inhibitor

SDS:

Sodium dodecylsulfate

NAC:

N-Acetyl-cysteine

rhEpo:

Human recombinant erythropoietin

PS:

Phosphatidylserine

DCFH-DA:

2′,7′-Dichlorofluorescin diacetate

PBS:

Phosphate-buffered saline

ROS:

Reactive oxygen species

GSH:

Reduced glutathione

CaI:

Calcium ionophore A23187

Hb:

Hemoglobin

BSA:

Bovine serum albumin

EMA:

Eosin-5-maleimide

P-Tyr:

Phosphotyrosine residue

N-Tyr:

Nitrotyrosine residue

CI:

Calpain inhibitor I

Aqp1:

Aquaporin 1

EpoR:

Erythropoietin receptor

PTP1B:

Phosphotyrosine phosphatase 1B

p-NPP:

p-Nitrophenylphosphate

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Acknowledgments

This work was supported by grants from the University of Buenos Aires (UBA), the National Council of Scientific and Technical Research (CONICET) and the National Agency for Scientific and Technologic Promotion (ANPCYT). Dr. Alcira Nesse and Dr. Daniela Vittori are research scientists at the National Council of Scientific and Technical Research (CONICET), and Lic. Daiana Vota has received a fellowship from CONICET (Argentina).

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Authors and Affiliations

  1. 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. Vota, Romina E. Maltaneri, Shirley D. Wenker, Alcira B. Nesse & Daniela C. Vittori

  2. Pabellón II, Piso 4, Ciudad Universitaria, C1428EHA, Buenos Aires, Argentina

    Daiana M. Vota, Romina E. Maltaneri, Shirley D. Wenker, Alcira B. Nesse & Daniela C. Vittori

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  1. Daiana M. Vota
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  2. Romina E. Maltaneri
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  3. Shirley D. Wenker
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  4. Alcira B. Nesse
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  5. Daniela C. Vittori
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Correspondence to Daniela C. Vittori.

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Vota, D.M., Maltaneri, R.E., Wenker, S.D. et al. Differential Erythropoietin Action upon Cells Induced to Eryptosis by Different Agents. Cell Biochem Biophys 65, 145–157 (2013). https://doi.org/10.1007/s12013-012-9408-4

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