Erythropoietin and Erythropoietin Receptors in Human CNS Neurons, Astrocytes, Microglia, and Oligodendrocytes Grown in Culture

Nagai, Atsushi; Nakagawa, Eiji; Choi, Hyun B.; Hatori, Kozo; Kobayashi, Shotai; Kim, Seung Up

doi:10.1093/jnen/60.4.386

Cited by 278 publications

(192 citation statements)

References 26 publications

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“…Histological localization of the radiolabel after injection of 125 IasialoEPO showed a specific neuronal pattern, e.g., in the hippocampus (see Fig. 6, which is published as supporting information on the PNAS web site, www.pnas.org), similar to the one observed with 125 I-rhEpo (data not shown) or by immunohistochemical localization of the EpoR (14,42,43).…”

Section: Resultssupporting

confidence: 64%

Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo

Erbayraktar

Grasso

Sfacteria

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

408

319

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Erythropoietin (EPO) is a tissue-protective cytokine preventing vascular spasm, apoptosis, and inflammatory responses. Although best known for its role in hematopoietic lineages, EPO also affects other tissues, including those of the nervous system. Enthusiasm for recombinant human erythropoietin (rhEPO) as a potential neuroprotective therapeutic must be tempered, however, by the knowledge it also enlarges circulating red cell mass and increases platelet aggregability. Here we examined whether erythropoietic and tissue-protective activities of rhEPO might be dissociated by a variation of the molecule. We demonstrate that asialoerythropoietin (asialoEPO), generated by total enzymatic desialylation of rhEPO, possesses a very short plasma half-life and is fully neuroprotective. In marked contrast with rhEPO, this molecule at doses and frequencies at which rhEPO exhibited erythropoiesis, did not increase the hematocrit of mice or rats. AsialoEPO appeared promptly within the cerebrospinal fluid after i.v. administration; intravenously administered radioiodine-labeled asialoEPO bound to neurons within the hippocampus and cortex in a pattern corresponding to the distribution of the EPO receptor. Most importantly, asialoEPO exhibits a broad spectrum of neuroprotective activities, as demonstrated in models of cerebral ischemia, spinal cord compression, and sciatic nerve crush. These data suggest that nonerythropoietic variants of rhEPO can cross the blood–brain barrier and provide neuroprotection.

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Section: Resultssupporting

confidence: 64%

Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo

Erbayraktar

Grasso

Sfacteria

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

408

319

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“…EPO mRNA expression was demonstrated only in human astrocytes, while EPOR expression was found in human neurons, astrocytes, and microglia. Neither EPO nor EPOR expression was found in OLs (Nagai et al 2001;Sugawa et al 2002). These reports are consistent with our present result which show an over 18-fold up-regulation of EPOR gene expression in type II astrocytes, but not OLs.…”

Section: Candidate Genes That May Contribute To Type II Astrocyte Fatsupporting

confidence: 92%

Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes

Wang

Zhou

et al. 2011

Tohoku J. Exp. Med.

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Oligodendrocyte precursor cells (OPCs) are bipotential progenitor cells that can differentiate into myelin-forming oligodendrocytes or functionally undetermined type II astrocytes. Transplantation of OPCs is an attractive therapy for demyelinating diseases. However, due to their bipotential differentiation potential, the majority of OPCs differentiate into astrocytes at transplanted sites. It is therefore important to understand the molecular mechanisms that regulate the transition from OPCs to oligodendrocytes or astrocytes. In this study, we isolated OPCs from the spinal cords of rat embryos (16 days old) and induced them to differentiate into oligodendrocytes or type II astrocytes in the absence or presence of 10% fetal bovine serum, respectively. RNAs were extracted from each cell population and hybridized to GeneChip with 28,700 rat genes. Using the criterion of fold change > 4 in the expression level, we identified 83 genes that were up-regulated and 89 genes that were down-regulated in oligodendrocytes, and 92 genes that were up-regulated and 86 that were down-regulated in type II astrocytes compared with OPCs. The up-regulated genes, such as activating transcription factor 3 and myelin basic protein in oligodendrocytes or claudin 11 in type II astrocytes, might contribute to OPC differentiation and represent constitutive components of oligodendrocytes or type II astrocytes. The down-regulated genes in both oligodendrocytes and type II astrocytes, such as transcription factor 19, might be involved in maintaining self-renewal and/or represent the property of OPCs. These results provide new insights into the elucidation of the molecular mechanisms, by which OPCs differentiate to oligodendrocytes or type II astrocytes.

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“…32,33 Presumably, this regulation is accomplished by specific proinflammatory cytokines, for example, TNF-alpha, IL-1 and IL-6. 34 Temporally, EPOR upregulation occurs first by 12 h, primarily in neurons and endothelial cells of the microcirculation, followed hours later by an increase in EPO by both astrocytes and neurons. 31 These effects are especially prominent in the penumbral (at risk) region surrounding injury.…”

Section: Epo As a Neuroprotective Agentmentioning

confidence: 99%

Erythropoietin as an antiapoptotic, tissue-protective cytokine

Ghezzi

Brines²

2004

Cell Death Differ

301

230

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Erythropoietin (EPO) increases the number of circulating erythrocytes primarily by preventing apoptosis of erythroid progenitors. In addition to this proerythroid action, results of recent studies show that systemically administered EPO is protective in vivo, in several animal models of neuronal injury. In vitro, EPO prevents neuronal apoptosis induced by a variety of stimuli. This review summarizes the neuroprotective actions of EPO and discusses the underlying mechanisms in terms of signal transduction pathways involved. The understanding of these mechanisms will help differentiate the neuroprotective actions of EPO from its role in the bone marrow.

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Erythropoietin and Erythropoietin Receptors in Human CNS Neurons, Astrocytes, Microglia, and Oligodendrocytes Grown in Culture

Cited by 278 publications

References 26 publications

Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo

Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo

Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes

Erythropoietin as an antiapoptotic, tissue-protective cytokine

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