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Erythropoietin protects red blood cells from TRAIL1-induced cell death during red blood cell transition in Xenopus laevis

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Abstract

In anuran amphibians, larval red blood cells (RBCs) are replaced by adult-type RBCs during metamorphosis. We previously showed that tumor necrosis factor-related apoptosis-inducing ligand 1 (TRAIL1) induces apoptosis in larval-, but not adult-type RBCs in Xenopus laevis. We also found that protein kinase C (PKC) activation is involved in establishing resistance to TRAIL1-induced apoptosis in adult-type RBCs. Here, we investigated whether erythropoietin (EPO), which induces PKC activation in mammalian erythroblasts, is involved in the RBC transition in X. laevis. RT-PCR analysis revealed that epo mRNA was upregulated in the lung, from the metamorphic climax (stage 60) onward. In an RBC culture system, EPO pretreatment significantly attenuated the TRAIL1-induced death of larval- and adult-type RBCs isolated from tadpoles and adults, probably due partly to PKC activation. In samples from froglets undergoing RBC transition, which included both larval- and adult-type RBCs, EPO exhibited a stronger protective effect on the adult-type than the larval-type RBCs. Newly differentiated RBCs isolated from tadpoles treated with a hemolytic reagent were more resistant to TRAIL1-induced cell death than non-treated controls. These results suggest that EPO functions to protect adult-type RBCs from TRAIL1-induced cell death during RBC transition, and that the protective effect might decrease as RBCs age.

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Abbreviations

RBC:

Red blood cell

EPO:

Erythropoietin

TRAIL:

Tumor necrosis factor-related apoptosis-inducing ligand

PKC:

Protein kinase C

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Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education Culture, Sports, Science, and Technology (M. I.), Kitasato University Research Grant for Young Researchers (K. T.).

Conflict of interest

The authors declare no competing financial interests.

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Authors and Affiliations

  1. Laboratory of Molecular Biology, Department of Biosciences, School of Science, Kitasato University, 1-15-1 Kitasato, Minamiku, Sagamihara, 252-0373, Japan

    Kei Tamura, Nobuhiko Takamatsu & Michihiko Ito

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  1. Kei Tamura
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  2. Nobuhiko Takamatsu
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  3. Michihiko Ito
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Correspondence to Kei Tamura.

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Tamura, K., Takamatsu, N. & Ito, M. Erythropoietin protects red blood cells from TRAIL1-induced cell death during red blood cell transition in Xenopus laevis . Mol Cell Biochem 398, 73–81 (2015). https://doi.org/10.1007/s11010-014-2206-0

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  • DOI: https://doi.org/10.1007/s11010-014-2206-0

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