Hypophosphorylation of ribosomal protein S6 is a molecular mechanism underlying ischemic tolerance induced by either hibernation or preconditioning

Shin Ichi Miyake, Hideaki Wakita, Joshua D. Bernstock, Paola Castri, Christl Ruetzler, Junko Miyake, Yang Ja Lee, John M. Hallenbeck

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) have an extraordinary capacity to withstand prolonged and profound reductions in blood flow and oxygen delivery to the brain without incurring any cellular damage. As such, the hibernation torpor of I. tridecemlineatus provides a valuable model of tolerance to ischemic stress. Herein, we report that during hibernation torpor, a marked reduction in the phosphorylation of the ribosomal protein S6 (rpS6) occurs within the brains of I. tridecemlineatus. Of note, rpS6 phosphorylation was shown to increase in the brains of rats that underwent an occlusion of the middle cerebral artery. However, such an increase was attenuated after the implementation of an ischemic preconditioning paradigm. In addition, cultured cortical neurons treated with the rpS6 kinase (S6K) inhibitors, d-glucosamine or PF4708671, displayed a decrease in rpS6 phosphorylation and a subsequent increase in tolerance to oxygen/glucose deprivation, an in vitro model of ischemic stroke. Collectively, such evidence suggests that the down-regulation of rpS6 signal transduction may account for a substantial part of the observed increase in cellular tolerance to brain ischemia that occurs during hibernation torpor and after ischemic preconditioning. Further identification and characterization of the mechanisms used by hibernating species to increase ischemic tolerance may eventually clarify how the loss of homeostatic control that occurs during and after cerebral ischemia in the clinic can ultimately be minimized and/or prevented.

Original languageEnglish
Pages (from-to)943-957
Number of pages15
JournalJournal of Neurochemistry
Volume135
Issue number5
DOIs
Publication statusPublished - 01-12-2015

Fingerprint

Ribosomal Protein S6
Hibernation
Torpor
Phosphorylation
Brain
Ischemic Preconditioning
Brain Ischemia
Ribosomal Protein S6 Kinases
Oxygen
Sciuridae
Signal transduction
Middle Cerebral Artery Infarction
Glucosamine
Neurons
Rats
Signal Transduction
Blood
Down-Regulation
Stroke
Glucose

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Miyake, Shin Ichi ; Wakita, Hideaki ; Bernstock, Joshua D. ; Castri, Paola ; Ruetzler, Christl ; Miyake, Junko ; Lee, Yang Ja ; Hallenbeck, John M. / Hypophosphorylation of ribosomal protein S6 is a molecular mechanism underlying ischemic tolerance induced by either hibernation or preconditioning. In: Journal of Neurochemistry. 2015 ; Vol. 135, No. 5. pp. 943-957.
@article{86422f85f7c04520ba97e2b0ec1ef09b,
title = "Hypophosphorylation of ribosomal protein S6 is a molecular mechanism underlying ischemic tolerance induced by either hibernation or preconditioning",
abstract = "Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) have an extraordinary capacity to withstand prolonged and profound reductions in blood flow and oxygen delivery to the brain without incurring any cellular damage. As such, the hibernation torpor of I. tridecemlineatus provides a valuable model of tolerance to ischemic stress. Herein, we report that during hibernation torpor, a marked reduction in the phosphorylation of the ribosomal protein S6 (rpS6) occurs within the brains of I. tridecemlineatus. Of note, rpS6 phosphorylation was shown to increase in the brains of rats that underwent an occlusion of the middle cerebral artery. However, such an increase was attenuated after the implementation of an ischemic preconditioning paradigm. In addition, cultured cortical neurons treated with the rpS6 kinase (S6K) inhibitors, d-glucosamine or PF4708671, displayed a decrease in rpS6 phosphorylation and a subsequent increase in tolerance to oxygen/glucose deprivation, an in vitro model of ischemic stroke. Collectively, such evidence suggests that the down-regulation of rpS6 signal transduction may account for a substantial part of the observed increase in cellular tolerance to brain ischemia that occurs during hibernation torpor and after ischemic preconditioning. Further identification and characterization of the mechanisms used by hibernating species to increase ischemic tolerance may eventually clarify how the loss of homeostatic control that occurs during and after cerebral ischemia in the clinic can ultimately be minimized and/or prevented.",
author = "Miyake, {Shin Ichi} and Hideaki Wakita and Bernstock, {Joshua D.} and Paola Castri and Christl Ruetzler and Junko Miyake and Lee, {Yang Ja} and Hallenbeck, {John M.}",
year = "2015",
month = "12",
day = "1",
doi = "10.1111/jnc.13368",
language = "English",
volume = "135",
pages = "943--957",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "5",

}

Hypophosphorylation of ribosomal protein S6 is a molecular mechanism underlying ischemic tolerance induced by either hibernation or preconditioning. / Miyake, Shin Ichi; Wakita, Hideaki; Bernstock, Joshua D.; Castri, Paola; Ruetzler, Christl; Miyake, Junko; Lee, Yang Ja; Hallenbeck, John M.

In: Journal of Neurochemistry, Vol. 135, No. 5, 01.12.2015, p. 943-957.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Hypophosphorylation of ribosomal protein S6 is a molecular mechanism underlying ischemic tolerance induced by either hibernation or preconditioning

AU - Miyake, Shin Ichi

AU - Wakita, Hideaki

AU - Bernstock, Joshua D.

AU - Castri, Paola

AU - Ruetzler, Christl

AU - Miyake, Junko

AU - Lee, Yang Ja

AU - Hallenbeck, John M.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) have an extraordinary capacity to withstand prolonged and profound reductions in blood flow and oxygen delivery to the brain without incurring any cellular damage. As such, the hibernation torpor of I. tridecemlineatus provides a valuable model of tolerance to ischemic stress. Herein, we report that during hibernation torpor, a marked reduction in the phosphorylation of the ribosomal protein S6 (rpS6) occurs within the brains of I. tridecemlineatus. Of note, rpS6 phosphorylation was shown to increase in the brains of rats that underwent an occlusion of the middle cerebral artery. However, such an increase was attenuated after the implementation of an ischemic preconditioning paradigm. In addition, cultured cortical neurons treated with the rpS6 kinase (S6K) inhibitors, d-glucosamine or PF4708671, displayed a decrease in rpS6 phosphorylation and a subsequent increase in tolerance to oxygen/glucose deprivation, an in vitro model of ischemic stroke. Collectively, such evidence suggests that the down-regulation of rpS6 signal transduction may account for a substantial part of the observed increase in cellular tolerance to brain ischemia that occurs during hibernation torpor and after ischemic preconditioning. Further identification and characterization of the mechanisms used by hibernating species to increase ischemic tolerance may eventually clarify how the loss of homeostatic control that occurs during and after cerebral ischemia in the clinic can ultimately be minimized and/or prevented.

AB - Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) have an extraordinary capacity to withstand prolonged and profound reductions in blood flow and oxygen delivery to the brain without incurring any cellular damage. As such, the hibernation torpor of I. tridecemlineatus provides a valuable model of tolerance to ischemic stress. Herein, we report that during hibernation torpor, a marked reduction in the phosphorylation of the ribosomal protein S6 (rpS6) occurs within the brains of I. tridecemlineatus. Of note, rpS6 phosphorylation was shown to increase in the brains of rats that underwent an occlusion of the middle cerebral artery. However, such an increase was attenuated after the implementation of an ischemic preconditioning paradigm. In addition, cultured cortical neurons treated with the rpS6 kinase (S6K) inhibitors, d-glucosamine or PF4708671, displayed a decrease in rpS6 phosphorylation and a subsequent increase in tolerance to oxygen/glucose deprivation, an in vitro model of ischemic stroke. Collectively, such evidence suggests that the down-regulation of rpS6 signal transduction may account for a substantial part of the observed increase in cellular tolerance to brain ischemia that occurs during hibernation torpor and after ischemic preconditioning. Further identification and characterization of the mechanisms used by hibernating species to increase ischemic tolerance may eventually clarify how the loss of homeostatic control that occurs during and after cerebral ischemia in the clinic can ultimately be minimized and/or prevented.

UR - http://www.scopus.com/inward/record.url?scp=84955322085&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84955322085&partnerID=8YFLogxK

U2 - 10.1111/jnc.13368

DO - 10.1111/jnc.13368

M3 - Article

VL - 135

SP - 943

EP - 957

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 5

ER -