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Article . 2017
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Journal of Cerebral Blood Flow & Metabolism
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Induction of the cell survival kinase Sgk1: A possible novel mechanism for α-phenyl-N-tert-butyl nitrone in experimental stroke

Authors: Catherine McCaig; Paris Ataliotis; Anan Shtaya; Ayan S Omar; A. Richard Green; Clive N Kind; Anthony C Pereira; +5 Authors

Induction of the cell survival kinase Sgk1: A possible novel mechanism for α-phenyl-N-tert-butyl nitrone in experimental stroke

Abstract

Nitrones (e.g. α-phenyl-N-tert-butyl nitrone; PBN) are cerebroprotective in experimental stroke. Free radical trapping is their proposed mechanism. As PBN has low radical trapping potency, we tested Sgk1 induction as another possible mechanism. PBN was injected (100 mg/kg, i.p.) into adult male rats and mice. Sgk1 was quantified in cerebral tissue by microarray, quantitative RT-PCR and western analyses. Sgk1+/+ and Sgk1−/− mice were randomized to receive PBN or saline immediately following transient (60 min) occlusion of the middle cerebral artery. Neurological deficit was measured at 24 h and 48 h and infarct volume at 48 h post-occlusion. Following systemic PBN administration, rapid induction of Sgk1 was detected by microarray (at 4 h) and confirmed by RT-PCR and phosphorylation of the Sgk1-specific substrate NDRG1 (at 6 h). PBN-treated Sgk1+/+ mice had lower neurological deficit ( p < 0.01) and infarct volume ( p < 0.01) than saline-treated Sgk1+/+ mice. PBN-treated Sgk1−/− mice did not differ from saline-treated Sgk1−/− mice. Saline-treated Sgk1−/− and Sgk1+/+ mice did not differ. Brain Sgk3:Sgk1 mRNA ratio was 1.0:10.6 in Sgk1+/+ mice. Sgk3 was not augmented in Sgk1−/− mice. We conclude that acute systemic treatment with PBN induces Sgk1 in brain tissue. Sgk1 may play a part in PBN-dependent actions in acute brain ischemia.

Country
United Kingdom
Subjects by Vocabulary

Microsoft Academic Graph classification: Radical trapping Stereochemistry α phenyl n tert butyl nitrone Neuroprotection Nitrone medicine Stroke Cell survival chemistry.chemical_classification Kinase Chemistry medicine.disease SGK1

Keywords

Male, Transcriptional Activation, Protein Serine-Threonine Kinases, Brain Ischemia, Immediate-Early Proteins, Cyclic N-Oxides, Mice, Animals, Acute stroke, Mice, Knockout, Brain, Infarction, Middle Cerebral Artery, Original Articles, lacunar infarcts, animal models, Rats, Stroke, Neurology, focal ischemia, Nitrogen Oxides, neuroprotection, Neurology (clinical), Cardiology and Cardiovascular Medicine

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10. Hainsworth AH, Bhuiyan N and Green AR. The nitrone disodium 2,4-sulphophenyl-N-tert-butylnitrone is without cytoprotective effect on sodium nitroprussideinduced cell death in N1E-115 neuroblastoma cells in vitro. J Cereb Blood Flow Metab 2008; 28: 24-28.

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    7
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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download
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
OpenAIRE UsageCountsViews provided by UsageCounts
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7
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1
31
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Funded by
UKRI| The Oxford Control Brain Collection
Project
  • Funder: UK Research and Innovation (UKRI)
  • Project Code: G1000691
  • Funding stream: MRC
,
NIH| Mechanism of sgk action in the collecting duct
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01DK058898-03
  • Funding stream: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
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