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Cited by 11Neurological Disorders and TreatmentsAcute Ischemic Stroke ManagementNeurological Disease Mechanisms and Treatments

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

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McCaig, Catherine, Ataliotis, Paris, Shtaya, Anan, Omar, Ayan S, Green, A Richard, Kind, Clive N, Pereira, Anthony C, Naray-Fejes-Toth, Aniko +4 more·2019·Journal of Cerebral Blood Flow & Metabolism
DOI 10.1177/0271678x17746980PMC PMC6545623
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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.

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Authors
McCaig, C., Ataliotis, P., Shtaya, A., Omar, A. S., Green, A. R., Kind, C. N., Pereira, A. C., Naray-Fejes-Toth, A., Fejes-Toth, G., Yáñez-Muñoz, R. J., Murray, J. T., & Hainsworth, A. H.
Affiliations
  • St George's, University of London (GB)
  • University of Nottingham (GB)
  • De Montfort University (GB)
  • National Health Service (GB)
  • Molecular & Systems Biology Department, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
  • AGCTlab.org, Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey, UK
  • Trinity College Dublin (IE)
Corresponding author
Hainsworth, Atticus H
ORCID
Venue
Journal of Cerebral Blood Flow & Metabolism
Publisher
SAGE Publications
Published
2017-12-20
Volume
39
Issue
6
Pages
1111-1121
ISSN
  • 0271-678X (ISSN-L)
  • 1559-7016
DOI
10.1177/0271678x17746980
PMC
PMC6545623
OpenAlex
W2781338425
Cited by
11
References
2
Citations by year
2026: 1 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 2
FWCI
0.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Cerebral Blood Flow & Metabolism (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • St George's Online Research Archive (St George's University of London) (acceptedVersion)
Funders
  • National Institute for Health and Care Research (CL-2015-16-001)
  • National Centre for the Replacement, Refinement and Reduction of Animals in Research (G0800701/1)
  • Medical Research Council (MR/L022656/1)
Topics
  • Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
SGK1, N-tert-butyl-alpha-phenylnitrone, nitrones, cerebral ischemia, stroke, SGK3, infarct size, neurological deficit, middle cerebral artery occlusion, neuroprotection
MeSH terms
Serum-Glucocorticoid Regulated Kinases, Animals, Brain, Brain Ischemia, Cyclic N-Oxides, Male, Nitrogen Oxides, Transcriptional Activation, Protein Serine-Threonine Kinases, Immediate-Early Proteins, Mice, Knockout, Infarction, Middle Cerebral Artery, Stroke, Mice, Rats

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