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dc.contributor.author
Palazzolo, Gemma
dc.contributor.author
Horvath, Peter
dc.contributor.author
Zenobi-Wong, Marcy
dc.date.accessioned
2018-08-02T08:27:37Z
dc.date.available
2017-06-10T12:11:43Z
dc.date.available
2018-08-02T08:27:37Z
dc.date.issued
2012-11-29
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0049979
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/60688
dc.identifier.doi
10.3929/ethz-b-000060688
dc.description.abstract
Background Neurite formation and synaptic patterning are fundamental to the development of a functional nervous system. Flavonoids are natural molecules known for having beneficial effects on brain health through diverse molecular pathways. Cytoskeletal changes occurring during neuritogenesis and synapse formation often involve Rho GTPases. Here we hypothesized that the flavonoid isoquercitrin promotes neuronal differentiation through Rho signalling. Methodology/Principal Findings We performed time lapse imaging of NG108-15 cells during incubation with/without isoquercitrin. Isoquercitrin stimulated extensive neurites enriched in the synaptic vesicle protein synaptotagmin-1. Neurite extension was augmented by the ROCK inhibitor Y-27632 suggesting an inactivation of RhoA/Rho kinase as the mechanism. To test this, we first measured the dose-dependent effect of isoquercitrin on RhoA activity and found a 47% reduction in RhoA activity at concentrations which induced neurites (≥40 µM). Secondly, we tested the ability of isoquercitrin to rescue the neural phenotype in a model of RhoA-induced neurite retraction and found that 40 µM isoquercitrin added to cultures previously treated with the RhoA activator calpeptin produced significantly more neurite length/cell than calpeptin alone. Finally, we tested the hypothesis that isoquercitrin may affect RhoA localization preventing the translocation to the plasma membrane. Unexpectedly, immunolocalization studies showed that RhoA was present in nuclear compartments of control NG108-cells, but underwent translocation to the cytoplasm upon treatment with isoquercitrin. DNA microarrays and reverse transcription - quantitative PCR (RT-qPCR) revealed differences in global gene expression of Rho GTPase family members. These data taken together indicate that isoquercitrin is a potential stimulator of neuronal differentiation, through multiple Rho GTPase mediated mechanisms. Conclusions/Significance As several members of the Rho GTPase family are implicated in human neurological disorders/injuries, our results suggest that isoquercitrin could be used in the treatment of these pathological states through its effect on this family of molecular switches.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/3.0/
dc.title
The Flavonoid Isoquercitrin Promotes Neurite Elongation by Reducing RhoA Activity
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 3.0 Unported
ethz.journal.title
PLoS ONE
ethz.journal.volume
7
en_US
ethz.journal.issue
11
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e49979
en_US
ethz.size
10 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.nebis
006206116
ethz.publication.place
Lawrence, Kan.
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02518 - Institut für Biomechanik / Institute for Biomechanics::03949 - Zenobi-Wong, Marcy / Zenobi-Wong, Marcy
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02518 - Institut für Biomechanik / Institute for Biomechanics::03949 - Zenobi-Wong, Marcy / Zenobi-Wong, Marcy
ethz.relation.isReferencedBy
https://doi.org/10.1371/annotation/c281cc87-1a2b-4a47-8930-6f6bca672b95
ethz.date.deposited
2017-06-10T12:12:14Z
ethz.source
ECIT
ethz.identifier.importid
imp59365026e8a2346718
ethz.ecitpid
pub:96966
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-18T15:14:19Z
ethz.rosetta.lastUpdated
2018-11-07T17:40:43Z
ethz.rosetta.versionExported
true
ethz.COinS
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