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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

Catherine McCaig, Paris Ataliotis, Anan Shtaya, Ayan S Omar, A Richard Green, Clive N Kind, Anthony C Pereira, Aniko Naray-Fejes-Toth, Geza Fejes-Toth, Rafael J Yáñez-Muñoz, James Murray Orcid Logo, Atticus H Hainsworth

Journal of Cerebral Blood Flow & Metabolism, Volume: 39, Issue: 6, Pages: 1111 - 1121

Swansea University Author: James Murray Orcid Logo

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DOI (Published version): 10.1177/0271678x17746980

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...

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Published in: Journal of Cerebral Blood Flow & Metabolism
ISSN: 0271-678X 1559-7016
Published: SAGE Publications 2019
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URI: https://cronfa.swan.ac.uk/Record/cronfa58771
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spelling 2021-12-03T15:25:43.9602322 v2 58771 2021-11-24 Induction of the cell survival kinase Sgk1: A possible novel mechanism for α-phenyl-N-tert-butyl nitrone in experimental stroke 12d0a585fcfe66f83c4c21c6bca3197b 0000-0002-6928-2347 James Murray James Murray true false 2021-11-24 MEDS 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. Journal Article Journal of Cerebral Blood Flow & Metabolism 39 6 1111 1121 SAGE Publications 0271-678X 1559-7016 Acute stroke, animal models, focal ischemia, lacunar infarcts, neuroprotection 1 6 2019 2019-06-01 10.1177/0271678x17746980 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University 2021-12-03T15:25:43.9602322 2021-11-24T13:55:18.7029506 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Catherine McCaig 1 Paris Ataliotis 2 Anan Shtaya 3 Ayan S Omar 4 A Richard Green 5 Clive N Kind 6 Anthony C Pereira 7 Aniko Naray-Fejes-Toth 8 Geza Fejes-Toth 9 Rafael J Yáñez-Muñoz 10 James Murray 0000-0002-6928-2347 11 Atticus H Hainsworth 12 58771__21780__e144c619fe274fdba758517985674bf2.pdf 58771.pdf 2021-12-03T15:24:04.6397463 Output 932414 application/pdf Version of Record true Copyright: Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License true eng http://www.creativecommons.org/licenses/by-nc/4.0/
title Induction of the cell survival kinase Sgk1: A possible novel mechanism for α-phenyl-N-tert-butyl nitrone in experimental stroke
spellingShingle Induction of the cell survival kinase Sgk1: A possible novel mechanism for α-phenyl-N-tert-butyl nitrone in experimental stroke
James Murray
title_short Induction of the cell survival kinase Sgk1: A possible novel mechanism for α-phenyl-N-tert-butyl nitrone in experimental stroke
title_full Induction of the cell survival kinase Sgk1: A possible novel mechanism for α-phenyl-N-tert-butyl nitrone in experimental stroke
title_fullStr Induction of the cell survival kinase Sgk1: A possible novel mechanism for α-phenyl-N-tert-butyl nitrone in experimental stroke
title_full_unstemmed Induction of the cell survival kinase Sgk1: A possible novel mechanism for α-phenyl-N-tert-butyl nitrone in experimental stroke
title_sort Induction of the cell survival kinase Sgk1: A possible novel mechanism for α-phenyl-N-tert-butyl nitrone in experimental stroke
author_id_str_mv 12d0a585fcfe66f83c4c21c6bca3197b
author_id_fullname_str_mv 12d0a585fcfe66f83c4c21c6bca3197b_***_James Murray
author James Murray
author2 Catherine McCaig
Paris Ataliotis
Anan Shtaya
Ayan S Omar
A Richard Green
Clive N Kind
Anthony C Pereira
Aniko Naray-Fejes-Toth
Geza Fejes-Toth
Rafael J Yáñez-Muñoz
James Murray
Atticus H Hainsworth
format Journal article
container_title Journal of Cerebral Blood Flow & Metabolism
container_volume 39
container_issue 6
container_start_page 1111
publishDate 2019
institution Swansea University
issn 0271-678X
1559-7016
doi_str_mv 10.1177/0271678x17746980
publisher SAGE Publications
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description 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.
published_date 2019-06-01T08:03:21Z
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