EV-3, an endogenous human erythropoietin isoform with distinct functional relevance
Abstract Generation of multiple mRNAs by alternative splicing is well known in the group of cytokines and has recently been reported for the human erythropoietin (EPO) gene. Here, we focus on the alternatively spliced EPO transcript characterized by deletion of exon 3 (hEPOΔ3). We show co-regulation...
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2017
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oai:doaj.org-article:a3a06994804a476ea95d8d6d579490d72021-12-02T12:32:27ZEV-3, an endogenous human erythropoietin isoform with distinct functional relevance10.1038/s41598-017-03167-02045-2322https://doaj.org/article/a3a06994804a476ea95d8d6d579490d72017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03167-0https://doaj.org/toc/2045-2322Abstract Generation of multiple mRNAs by alternative splicing is well known in the group of cytokines and has recently been reported for the human erythropoietin (EPO) gene. Here, we focus on the alternatively spliced EPO transcript characterized by deletion of exon 3 (hEPOΔ3). We show co-regulation of EPO and hEPOΔ3 in human diseased tissue. The expression of hEPOΔ3 in various human samples was low under normal conditions, and distinctly increased in pathological states. Concomitant up-regulation of hEPOΔ3 and EPO in response to hypoxic conditions was also observed in HepG2 cell cultures. Using LC-ESI-MS/MS, we provide first evidence for the existence of hEPOΔ3 derived protein EV-3 in human serum from healthy donors. Contrary to EPO, recombinant EV-3 did not promote early erythroid progenitors in cultures of human CD34+ haematopoietic stem cells. Repeated intraperitoneal administration of EV-3 in mice did not affect the haematocrit. Similar to EPO, EV-3 acted anti-apoptotic in rat hippocampal neurons exposed to oxygen-glucose deprivation. Employing the touch-screen paradigm of long-term visual discrimination learning, we obtained first in vivo evidence of beneficial effects of EV-3 on cognition. This is the first report on the presence of a naturally occurring EPO protein isoform in human serum sharing non-erythropoietic functions with EPO.Christel BonnasLiane WüstefeldDaniela WinklerRomy Kronstein-WiedemannEkrem DereKatja SpechtMelanie BoxbergTorsten TonnHannelore EhrenreichHerbert StadlerInge SillaberNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017) |
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Medicine R Science Q |
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Medicine R Science Q Christel Bonnas Liane Wüstefeld Daniela Winkler Romy Kronstein-Wiedemann Ekrem Dere Katja Specht Melanie Boxberg Torsten Tonn Hannelore Ehrenreich Herbert Stadler Inge Sillaber EV-3, an endogenous human erythropoietin isoform with distinct functional relevance |
| description |
Abstract Generation of multiple mRNAs by alternative splicing is well known in the group of cytokines and has recently been reported for the human erythropoietin (EPO) gene. Here, we focus on the alternatively spliced EPO transcript characterized by deletion of exon 3 (hEPOΔ3). We show co-regulation of EPO and hEPOΔ3 in human diseased tissue. The expression of hEPOΔ3 in various human samples was low under normal conditions, and distinctly increased in pathological states. Concomitant up-regulation of hEPOΔ3 and EPO in response to hypoxic conditions was also observed in HepG2 cell cultures. Using LC-ESI-MS/MS, we provide first evidence for the existence of hEPOΔ3 derived protein EV-3 in human serum from healthy donors. Contrary to EPO, recombinant EV-3 did not promote early erythroid progenitors in cultures of human CD34+ haematopoietic stem cells. Repeated intraperitoneal administration of EV-3 in mice did not affect the haematocrit. Similar to EPO, EV-3 acted anti-apoptotic in rat hippocampal neurons exposed to oxygen-glucose deprivation. Employing the touch-screen paradigm of long-term visual discrimination learning, we obtained first in vivo evidence of beneficial effects of EV-3 on cognition. This is the first report on the presence of a naturally occurring EPO protein isoform in human serum sharing non-erythropoietic functions with EPO. |
| format |
article |
| author |
Christel Bonnas Liane Wüstefeld Daniela Winkler Romy Kronstein-Wiedemann Ekrem Dere Katja Specht Melanie Boxberg Torsten Tonn Hannelore Ehrenreich Herbert Stadler Inge Sillaber |
| author_facet |
Christel Bonnas Liane Wüstefeld Daniela Winkler Romy Kronstein-Wiedemann Ekrem Dere Katja Specht Melanie Boxberg Torsten Tonn Hannelore Ehrenreich Herbert Stadler Inge Sillaber |
| author_sort |
Christel Bonnas |
| title |
EV-3, an endogenous human erythropoietin isoform with distinct functional relevance |
| title_short |
EV-3, an endogenous human erythropoietin isoform with distinct functional relevance |
| title_full |
EV-3, an endogenous human erythropoietin isoform with distinct functional relevance |
| title_fullStr |
EV-3, an endogenous human erythropoietin isoform with distinct functional relevance |
| title_full_unstemmed |
EV-3, an endogenous human erythropoietin isoform with distinct functional relevance |
| title_sort |
ev-3, an endogenous human erythropoietin isoform with distinct functional relevance |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/a3a06994804a476ea95d8d6d579490d7 |
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