PERK is responsible for the increased phosphorylation of eIF2α and the severe inhibition of protein synthesis after transient global brain ischemia

Cheri R. Owen, Rita Kumar, Peichuan Zhang, Barbara Claire McGrath, Douglas R. Cavener, Gary S. Krause

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Reperfusion after global brain ischemia results initially in a widespread suppression of protein synthesis in neurons that is due to inhibition of translation initiation as a result of the phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2). To address the role of the eIF2α kinase RNA-dependent protein kinase-like endoplasmic reticulum kinase (PERK) in the reperfused brain, transgenic mice with a targeted disruption of the Perk gene were subjected to 20 min of forebrain ischemia followed by 10 min of reperfusion. In wild-type mice, phosphorylated eIF2α was detected in the non-ischemic brain and its levels were elevated threefold after 10 min of reperfusion. Conversely, there was no phosphorylated eIF2α detected in the non-ischemic transgenic mice and there was no sizeable rise in phosphorylated eIF2α levels in the forebrain after ischemia and reperfusion. Moreover, there was a substantial rescue of protein translation in the reperfused transgenic mice. Neither group showed any change in total eIF2α, phosphorylated eukaryotic elongation factor 2 or total eukaryotic elongation factor 2 levels. These data demonstrate that PERK is responsible for the large increase in phosphorylated eIF2α and the suppression of translation early in reperfusion after transient global brain ischemia.

Original languageEnglish (US)
Pages (from-to)1235-1242
Number of pages8
JournalJournal of Neurochemistry
Volume94
Issue number5
DOIs
StatePublished - Aug 1 2005

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Eukaryotic Initiation Factor-2
Phosphorylation
Brain Ischemia
Endoplasmic Reticulum
Protein Kinases
Brain
Phosphotransferases
Reperfusion
Peptide Elongation Factor 2
Proteins
Transgenic Mice
Prosencephalon
Ischemia
eIF-2 Kinase
Protein Biosynthesis
Neurons
Genes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

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title = "PERK is responsible for the increased phosphorylation of eIF2α and the severe inhibition of protein synthesis after transient global brain ischemia",
abstract = "Reperfusion after global brain ischemia results initially in a widespread suppression of protein synthesis in neurons that is due to inhibition of translation initiation as a result of the phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2). To address the role of the eIF2α kinase RNA-dependent protein kinase-like endoplasmic reticulum kinase (PERK) in the reperfused brain, transgenic mice with a targeted disruption of the Perk gene were subjected to 20 min of forebrain ischemia followed by 10 min of reperfusion. In wild-type mice, phosphorylated eIF2α was detected in the non-ischemic brain and its levels were elevated threefold after 10 min of reperfusion. Conversely, there was no phosphorylated eIF2α detected in the non-ischemic transgenic mice and there was no sizeable rise in phosphorylated eIF2α levels in the forebrain after ischemia and reperfusion. Moreover, there was a substantial rescue of protein translation in the reperfused transgenic mice. Neither group showed any change in total eIF2α, phosphorylated eukaryotic elongation factor 2 or total eukaryotic elongation factor 2 levels. These data demonstrate that PERK is responsible for the large increase in phosphorylated eIF2α and the suppression of translation early in reperfusion after transient global brain ischemia.",
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PERK is responsible for the increased phosphorylation of eIF2α and the severe inhibition of protein synthesis after transient global brain ischemia. / Owen, Cheri R.; Kumar, Rita; Zhang, Peichuan; McGrath, Barbara Claire; Cavener, Douglas R.; Krause, Gary S.

In: Journal of Neurochemistry, Vol. 94, No. 5, 01.08.2005, p. 1235-1242.

Research output: Contribution to journalArticle

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