An extra high dose of erythropoietin fails to support the proliferation of erythropoietin dependent cell lines

Erythropoietin is responsible for the red blood cell formation by stimulating the proliferation and the differentiation of erythroid precursor cells. Erythropoietin triggers the conformational change in its receptor thereby induces the phosphorylation of JAK2. In this study, we show that an extra hi...

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Bibliographic Details
Published in:Cytotechnology (Dordrecht) 2011-03, Vol.63 (2), p.101-109
Main Authors: Abe, Satoshi, Sasaki, Ryuzo, Masuda, Seiji
Format: Article
Language:English
Subjects:
Antibodies
Apoptosis
Binding sites
Biochemistry
Biological and medical sciences
Biomedicine
Biotechnology
Cell culture
Cell differentiation
Cell growth
Cell lines
Cell proliferation
Chemistry
Chemistry and Materials Science
DNA fragmentation
Erythrocytes
Erythropoietin
Fundamental and applied biological sciences. Psychology
JAACT Special Issue
Janus kinase 2
Kinases
Phosphorylation
Proteins
Signal transduction
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Summary:Erythropoietin is responsible for the red blood cell formation by stimulating the proliferation and the differentiation of erythroid precursor cells. Erythropoietin triggers the conformational change in its receptor thereby induces the phosphorylation of JAK2. In this study, we show that an extra high dose of erythropoietin, however, fails to activate the erythropoietin receptor, to stimulate the phosphorylation of JAK2 and to support the cell proliferation of Ep-FDC-P2 cell. Moreover, high dose of EPO also inhibited the proliferation of various erythropoietin-dependent cell lines, suggesting that excess amount of EPO could not trigger the conformational change of the receptor. In the presence of an extra high dose of erythropoietin as well as in the absence of erythropoietin, the cells caused the DNA fragmentation, a typical symptom of apoptosis. The impairment of cell growth and the DNA fragmentation at the extremely high concentration of EPO was rescued by the addition of erythropoietin antibody or soluble form of erythropoietin receptor by titrating the excess erythropoietin. These results suggest that two erythropoietin binding sites on erythropoietin receptor dimer should be occupied by a single erythropoietin molecule for the proper conformational change of the receptor and the signal transduction of erythropoietin, instead, when two erythropoietin binding sites on the receptor are shared by two erythropoietin molecules, it fails to evoke the conformational change of erythropoietin receptor adequate for signal transduction.
ISSN:0920-9069
1573-0778
DOI:10.1007/s10616-011-9345-x