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dc.contributor.authorWei, S
dc.contributor.authorLow, SW
dc.contributor.authorPoore, CP
dc.contributor.authorChen, B
dc.contributor.authorGao, Y
dc.contributor.authorNilius, B
dc.contributor.authorLiao, P
dc.date.accessioned2020-11-12T00:39:19Z
dc.date.available2020-11-12T00:39:19Z
dc.date.issued2020
dc.identifier.issn2296-634X
dc.identifier.doi10.3389/fcell.2020.562584
dc.identifier.urihttp://hdl.handle.net/10072/399227
dc.description.abstractIn stroke and other neurological diseases, Transient Receptor Potential Melastatin 4 (TRPM4) has been reported to cause oncotic cell death which is due to an excessive influx of sodium ions. Following stroke, hypoxia condition activates TRPM4 channel, and the sodium influx via TRPM4 is further enhanced by an increased TRPM4 expression. However, the effect of TRPM4 inhibition on oncotic cell death, particularly during the acute stage, remains largely unknown. Recently, we have developed a polyclonal antibody M4P that specifically inhibits TRPM4 channel. M4P blocks the channel via binding to a region close to the channel pore from extracellular space. Using M4P, we evaluated the acute effect of blocking TRPM4 in neurons, astrocytes, and vascular endothelial cells. In a rat stroke model, M4P co-localized with neuronal marker NeuN and endothelial marker vWF, whereas few GFAP positive astrocytes were stained by M4P in the ipsilateral hemisphere. When ATP was acutely depleted in cultured cortical neurons and microvascular endothelial cells, cell swelling was induced. Application of M4P significantly blocked TRPM4 current and attenuated oncosis. TUNEL assay, PI staining and western blot on cleaved Caspase-3 revealed that M4P could ameliorate apoptosis after 24 h hypoxia exposure. In contrast, acute ATP depletion in cultured astrocytes failed to demonstrate an increase of cell volume, and application of M4P or control IgG had no effect on cell volume change. When TRPM4 was overexpressed in astrocytes, acute ATP depletion successfully induced oncosis which could be suppressed by M4P treatment. Our results demonstrate that comparing to astrocytes, neurons, and vascular endothelial cells are more vulnerable to hypoxic injury. During the acute stage of stroke, blocking TRPM4 channel could protect neurons and vascular endothelial cells from oncotic cell death.
dc.description.peerreviewedYes
dc.publisherFrontiers Media
dc.relation.ispartofjournalFrontiers in Cell and Developmental Biology
dc.relation.ispartofvolume8
dc.subject.fieldofresearchCardiovascular medicine and haematology
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchcode3201
dc.subject.fieldofresearchcode3202
dc.titleComparison of Anti-oncotic Effect of TRPM4 Blocking Antibody in Neuron, Astrocyte and Vascular Endothelial Cell Under Hypoxia
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationWei, S; Low, SW; Poore, CP; Chen, B; Gao, Y; Nilius, B; Liao, P, Comparison of Anti-oncotic Effect of TRPM4 Blocking Antibody in Neuron, Astrocyte and Vascular Endothelial Cell Under Hypoxia, Frontiers in Cell and Developmental Biology, 2020, 8
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2020-11-12T00:18:15Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2020 Wei, Low, Poore, Chen, Gao, Nilius and Liao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
gro.hasfulltextFull Text
gro.griffith.authorNilius, Bernd


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