Protein kinase C epsilon activation delays neuronal depolarization during cardiac arrest in the euthermic arctic ground squirrel
Abstract During the pre‐hibernation season, arctic ground squirrels (AGS) can tolerate 8 min of asphyxial cardiac arrest (CA) without detectable brain pathology. Better understanding of the mechanisms regulating innate ischemia tolerance in AGS has the potential to facilitate the development of nove...
Published in: | Journal of Neurochemistry |
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crwiley:10.1111/j.1471-4159.2009.06196.x 2024-09-30T14:28:32+00:00 Protein kinase C epsilon activation delays neuronal depolarization during cardiac arrest in the euthermic arctic ground squirrel Dave, Kunjan R. Anthony DeFazio, Richard Raval, Ami P. Dashkin, Oleksandr Saul, Isabel Iceman, Kimberly E. Perez‐Pinzon, Miguel A. Drew, Kelly L. 2009 http://dx.doi.org/10.1111/j.1471-4159.2009.06196.x https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1471-4159.2009.06196.x https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1471-4159.2009.06196.x en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor Journal of Neurochemistry volume 110, issue 4, page 1170-1179 ISSN 0022-3042 1471-4159 journal-article 2009 crwiley https://doi.org/10.1111/j.1471-4159.2009.06196.x 2024-09-05T05:08:35Z Abstract During the pre‐hibernation season, arctic ground squirrels (AGS) can tolerate 8 min of asphyxial cardiac arrest (CA) without detectable brain pathology. Better understanding of the mechanisms regulating innate ischemia tolerance in AGS has the potential to facilitate the development of novel prophylactic agents to induce ischemic tolerance in patients at risk of stroke or CA. We hypothesized that neuroprotection in AGS involves robust maintenance of ion homeostasis similar to anoxia‐tolerant turtles. Ion homeostasis was assessed by monitoring ischemic depolarization (ID) in cerebral cortex during CA in vivo and during oxygen glucose deprivation in vitro in acutely prepared hippocampal slices. In both models, the onset of ID was significantly delayed in AGS compared with rats. The epsilon protein kinase C (εPKC) is a key mediator of neuroprotection and inhibits both Na + /K + ‐ATPase and voltage‐gated sodium channels, primary mediators of the collapse of ion homeostasis during ischemia. The selective peptide inhibitor of εPKC (εV1‐2) shortened the time to ID in brain slices from AGS but not in rats despite evidence that εV1‐2 decreased activation of εPKC in brain slices from both rats and AGS. These results support the hypothesis that εPKC activation delays the collapse of ion homeostasis during ischemia in AGS. Article in Journal/Newspaper Arctic ground squirrel Arctic Wiley Online Library Arctic Journal of Neurochemistry 110 4 1170 1179 |
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Open Polar |
collection |
Wiley Online Library |
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crwiley |
language |
English |
description |
Abstract During the pre‐hibernation season, arctic ground squirrels (AGS) can tolerate 8 min of asphyxial cardiac arrest (CA) without detectable brain pathology. Better understanding of the mechanisms regulating innate ischemia tolerance in AGS has the potential to facilitate the development of novel prophylactic agents to induce ischemic tolerance in patients at risk of stroke or CA. We hypothesized that neuroprotection in AGS involves robust maintenance of ion homeostasis similar to anoxia‐tolerant turtles. Ion homeostasis was assessed by monitoring ischemic depolarization (ID) in cerebral cortex during CA in vivo and during oxygen glucose deprivation in vitro in acutely prepared hippocampal slices. In both models, the onset of ID was significantly delayed in AGS compared with rats. The epsilon protein kinase C (εPKC) is a key mediator of neuroprotection and inhibits both Na + /K + ‐ATPase and voltage‐gated sodium channels, primary mediators of the collapse of ion homeostasis during ischemia. The selective peptide inhibitor of εPKC (εV1‐2) shortened the time to ID in brain slices from AGS but not in rats despite evidence that εV1‐2 decreased activation of εPKC in brain slices from both rats and AGS. These results support the hypothesis that εPKC activation delays the collapse of ion homeostasis during ischemia in AGS. |
format |
Article in Journal/Newspaper |
author |
Dave, Kunjan R. Anthony DeFazio, Richard Raval, Ami P. Dashkin, Oleksandr Saul, Isabel Iceman, Kimberly E. Perez‐Pinzon, Miguel A. Drew, Kelly L. |
spellingShingle |
Dave, Kunjan R. Anthony DeFazio, Richard Raval, Ami P. Dashkin, Oleksandr Saul, Isabel Iceman, Kimberly E. Perez‐Pinzon, Miguel A. Drew, Kelly L. Protein kinase C epsilon activation delays neuronal depolarization during cardiac arrest in the euthermic arctic ground squirrel |
author_facet |
Dave, Kunjan R. Anthony DeFazio, Richard Raval, Ami P. Dashkin, Oleksandr Saul, Isabel Iceman, Kimberly E. Perez‐Pinzon, Miguel A. Drew, Kelly L. |
author_sort |
Dave, Kunjan R. |
title |
Protein kinase C epsilon activation delays neuronal depolarization during cardiac arrest in the euthermic arctic ground squirrel |
title_short |
Protein kinase C epsilon activation delays neuronal depolarization during cardiac arrest in the euthermic arctic ground squirrel |
title_full |
Protein kinase C epsilon activation delays neuronal depolarization during cardiac arrest in the euthermic arctic ground squirrel |
title_fullStr |
Protein kinase C epsilon activation delays neuronal depolarization during cardiac arrest in the euthermic arctic ground squirrel |
title_full_unstemmed |
Protein kinase C epsilon activation delays neuronal depolarization during cardiac arrest in the euthermic arctic ground squirrel |
title_sort |
protein kinase c epsilon activation delays neuronal depolarization during cardiac arrest in the euthermic arctic ground squirrel |
publisher |
Wiley |
publishDate |
2009 |
url |
http://dx.doi.org/10.1111/j.1471-4159.2009.06196.x https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1471-4159.2009.06196.x https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1471-4159.2009.06196.x |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic ground squirrel Arctic |
genre_facet |
Arctic ground squirrel Arctic |
op_source |
Journal of Neurochemistry volume 110, issue 4, page 1170-1179 ISSN 0022-3042 1471-4159 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1111/j.1471-4159.2009.06196.x |
container_title |
Journal of Neurochemistry |
container_volume |
110 |
container_issue |
4 |
container_start_page |
1170 |
op_container_end_page |
1179 |
_version_ |
1811634164039942144 |