title: Erythropoietin protects red blood cells from TRAIL1-induced cell death during red blood cell transition in Xenopus laevis.
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.
authors.affiliation: Laboratory of Molecular Biology, Department of Biosciences, School of Science, Kitasato University, 1-15-1 Kitasato, Minamiku, Sagamihara, 252-0373, Japan, ktamura@sci.kitasato-u.ac.jp.
authors.forename: Kei
authors.initials: K
authors.lastname: Tamura
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Takamatsu
authors.forename: Michihiko
authors.initials: M
authors.lastname: Ito
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D004921:Erythropoietin / Q000235:genetics / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D008168:Lung / Q000254:growth & development / Q000378:metabolism; D008675:Metamorphosis, Biological; D020011:Protective Agents / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D013997:Time Factors; D029867:Xenopus Proteins / Q000235:genetics / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: D020011:Protective Agents; D053221:TNF-Related Apoptosis-Inducing Ligand; D029867:Xenopus Proteins; D004921:Erythropoietin; D011493:Protein Kinase C