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 language | English (US) |
|---|---|
| Pages (from-to) | 1235-1242 |
| Number of pages | 8 |
| Journal | Journal of Neurochemistry |
| Volume | 94 |
| Issue number | 5 |
| DOIs | |
| State | Published - Aug 1 2005 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Cellular and Molecular Neuroscience
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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 journal › Article
TY - JOUR
T1 - PERK is responsible for the increased phosphorylation of eIF2α and the severe inhibition of protein synthesis after transient global brain ischemia
AU - Owen, Cheri R.
AU - Kumar, Rita
AU - Zhang, Peichuan
AU - McGrath, Barbara Claire
AU - Cavener, Douglas R.
AU - Krause, Gary S.
PY - 2005/8/1
Y1 - 2005/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=24144440965&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=24144440965&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2005.03276.x
DO - 10.1111/j.1471-4159.2005.03276.x
M3 - Article
C2 - 16000157
AN - SCOPUS:24144440965
VL - 94
SP - 1235
EP - 1242
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 5
ER -