Miljus, Natasa

[["dc.bibliographiccitation.firstpage","218"],["dc.bibliographiccitation.journal","Neuroscience"],["dc.bibliographiccitation.lastpage","227"],["dc.contributor.author","Miljus, Natasa"],["dc.contributor.author","Heibeck, Saskia"],["dc.contributor.author","Jarrar, Miriam"],["dc.contributor.author","Micke, Michaele"],["dc.contributor.author","Ostrowski, Daniela"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Heinrich, Ralf"],["dc.date.accessioned","2017-09-07T11:45:43Z"],["dc.date.available","2017-09-07T11:45:43Z"],["dc.date.issued","2014"],["dc.description.abstract","The cytokine erythropoietin (Epo) initiates adaptive cellular responses to both moderate environmental challenges and tissue damaging insults in various non-hematopoietic mammalian tissues including the nervous system. Neuroprotective and neuroregenerative functions of Epo in mammals are mediated through receptor-associated Janus kinase 2 and intracellular signaling cascades that modify the transcription of Epo-regulated genes. Signal transducers and activators of transcription (STAT) and phosphoinositol-3-kinase (PI3K) represent key components of two important Epo-induced transduction pathways.Our previous study on insects revealed neuroprotective and regenerative functions of recombinant human Epo (rhEpo) similar to those in mammalian nervous tissues. Here we demonstrate that rhEpo effectively rescues primary cultured locust brain neurons from apoptotic cell death induced by hypoxia or the chemical compound H-7. The Janus kinase inhibitor AG-490 and the STAT inhibitor sc-355797 abolished protective effects of rhEpo on locust brain neurons. In contrast, inhibition of PI3K with LY294002 had no effect on rhEpo-mediated neuroprotection. The results indicate that rhEpo mediates the protection of locust brain neurons through interference with apoptotic pathways by the activation of a Janus kinase-associated receptor and STAT transcription factor(s). The involvement of similar transduction pathways in mammals and insects for the mediation of neuroprotection and support of neural regeneration by Epo indicates that an Epo/Epo receptor-like signaling system with high structural and functional similarity exists in both groups of animals. Epo-like signaling involved in tissue protection appears to be an ancient beneficial function shared by vertebrates and invertebrates."],["dc.identifier.doi","10.1016/j.neuroscience.2013.11.020"],["dc.identifier.gro","3150422"],["dc.identifier.pmid","24269933"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7184"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.title","Erythropoietin-mediated protection of insect brain neurons involves JAK and STAT but not PI3K transduction pathways"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","63"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","74"],["dc.bibliographiccitation.volume","141"],["dc.contributor.author","Miljus, Natasa"],["dc.contributor.author","Massih, Bita"],["dc.contributor.author","Weis, Marissa A."],["dc.contributor.author","Rison, Jan Vincent"],["dc.contributor.author","Bonnas, Christel B."],["dc.contributor.author","Sillaber, Inge"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Geurten, Bart R. H."],["dc.contributor.author","Heinrich, Ralf"],["dc.date.accessioned","2018-11-07T10:25:45Z"],["dc.date.available","2018-11-07T10:25:45Z"],["dc.date.issued","2017"],["dc.description.abstract","Erythropoietin (Epo) plays a dual role as an erythropoiesis-stimulating hormone and a locally produced cytoprotectant in various vertebrate tissues. Splice variants and engineered derivatives of Epo that mediate neuroprotection but do not stimulate erythropoiesis suggest that alternative receptors, different from the classical' homodimeric receptor involved in haematopoiesis, mediate neuroprotective Epo functions. Previous studies on grasshoppers demonstrated neuroprotective and neuroregenerative effects of Epo that involved similar transduction pathways as in mammals. To advance the characterization of yet unidentified neuroprotective Epo receptors, we studied the neuroprotective potency of the human non-erythropoietic Epo splice variant EV-3 in primary cultured locust brain neurons. We demonstrate that EV-3, like Epo, protects locust neurons from hypoxia-induced apoptotic death through activation of the Janus kinase/signal transducer and activator of transcription transduction pathway. Using the fluorescent dye FM1-43 to quantify endocytotic activity we show that both Epo and EV-3 increase the number of fluorescently labelled endocytotic vesicles. This reveals that binding of Epo to its neuroprotective receptor induces endocytosis, as it has been described for the mammalian homodimeric Epo-receptor expressed by erythroid progenitors. Reduction in Epo-stimulated endocytotic activity following pre-exposure to EV-3 indicated that both Epo and its splice variant bind to the same receptor on locust neurons. The shared neuroprotective potency of Epo and EV-3 in insect and mammalian neurons, in the absence of erythropoietic effects of EV-3 in mammals, suggests a greater similarity of the unidentified nervous Epo receptors (or receptor complexes) across phyla than between mammalian haematopoietic and neuroprotective receptors. Insects may serve as suitable models to evaluate the specific protective mechanisms mediated by Epo and its variants in non-erythropoietic mammalian tissues."],["dc.identifier.doi","10.1111/jnc.13967"],["dc.identifier.isi","000397502400006"],["dc.identifier.pmid","28142212"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42919"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley"],["dc.relation.issn","1471-4159"],["dc.relation.issn","0022-3042"],["dc.title","Neuroprotection and endocytosis: erythropoietin receptors in insect nervous systems"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]