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Activation of the extracellular signal-regulated protein kinase cascade in the hippocampal CA1 region in a rat model of global cerebral ischemic preconditioning

Shamloo, M. LU ; Rytter, A. LU and Wieloch, T. LU (1999) In Neuroscience 93(1). p.81-88
Abstract

A short period of sublethal preconditioning ischemia (3 min) followed by two days of reperfusion provides almost complete protection against ischemic cell death induced by a second (9 min) lethal ischemic episode. Here, we have investigated the extracellular signal-regulated protein kinase kinase and extracellular signal-regulated protein kinase, two kinases known to activate gene transcription and to be of importance for cell survival, after sublethal preconditioning ischemia in the rat hippocampal CA1 region. The activation levels of these two kinases were also studied after a second ischemic episode both in preconditioned and nonconditioned brains. An increased phosphorylation of the extracellular signal-regulated protein kinase... (More)

A short period of sublethal preconditioning ischemia (3 min) followed by two days of reperfusion provides almost complete protection against ischemic cell death induced by a second (9 min) lethal ischemic episode. Here, we have investigated the extracellular signal-regulated protein kinase kinase and extracellular signal-regulated protein kinase, two kinases known to activate gene transcription and to be of importance for cell survival, after sublethal preconditioning ischemia in the rat hippocampal CA1 region. The activation levels of these two kinases were also studied after a second ischemic episode both in preconditioned and nonconditioned brains. An increased phosphorylation of the extracellular signal-regulated protein kinase kinase was found in neuronal cell bodies, particularly in the nucleus, 30 min, 4 h and two days of reperfusion after preconditioning ischemia. Two days after preconditioning ischemia both extracellular signal-regulated protein kinase kinase and extracellular signal-regulated protein kinase were markedly phosphorylated. During the early reperfusion period (30 min) after the second ischemic insult the phosphorylation levels of these two kinases were increased in both nonconditioned and preconditioned brains. In the late reperfusion time (one day), the phosphorylation levels of the extracellular signal-regulated protein kinase kinase and extracellular signal-regulated protein kinase were decreased in preconditioned brains, but remained elevated in nonconditioned brains. We conclude that phosphorylation of the extracellular signal-regulated protein kinase kinase and extracellular signal-regulated protein kinase after sublethal ischemia correlates with the neuroprotection induced by preconditioning, possibly by transcriptional activation of neuroprotective genes. Also, preconditioning enhances normalization of the disturbed cell signaling through the extracellular signal-regulated protein kinase cascade induced by lethal ischemia.

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author
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organization
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type
Contribution to journal
publication status
published
subject
keywords
Brain ischemia, Cell death, Cell signaling, MAP kinase, Preconditioning, Tolerance
in
Neuroscience
volume
93
issue
1
pages
8 pages
publisher
Elsevier
external identifiers
  • pmid:10430472
  • scopus:0033028971
ISSN
0306-4522
DOI
10.1016/S0306-4522(99)00137-2
language
English
LU publication?
yes
id
c7f4a669-15a2-4371-bee7-f46f8ecbb98a
date added to LUP
2019-06-13 16:54:08
date last changed
2024-07-23 21:18:49
@article{c7f4a669-15a2-4371-bee7-f46f8ecbb98a,
  abstract     = {{<p>A short period of sublethal preconditioning ischemia (3 min) followed by two days of reperfusion provides almost complete protection against ischemic cell death induced by a second (9 min) lethal ischemic episode. Here, we have investigated the extracellular signal-regulated protein kinase kinase and extracellular signal-regulated protein kinase, two kinases known to activate gene transcription and to be of importance for cell survival, after sublethal preconditioning ischemia in the rat hippocampal CA1 region. The activation levels of these two kinases were also studied after a second ischemic episode both in preconditioned and nonconditioned brains. An increased phosphorylation of the extracellular signal-regulated protein kinase kinase was found in neuronal cell bodies, particularly in the nucleus, 30 min, 4 h and two days of reperfusion after preconditioning ischemia. Two days after preconditioning ischemia both extracellular signal-regulated protein kinase kinase and extracellular signal-regulated protein kinase were markedly phosphorylated. During the early reperfusion period (30 min) after the second ischemic insult the phosphorylation levels of these two kinases were increased in both nonconditioned and preconditioned brains. In the late reperfusion time (one day), the phosphorylation levels of the extracellular signal-regulated protein kinase kinase and extracellular signal-regulated protein kinase were decreased in preconditioned brains, but remained elevated in nonconditioned brains. We conclude that phosphorylation of the extracellular signal-regulated protein kinase kinase and extracellular signal-regulated protein kinase after sublethal ischemia correlates with the neuroprotection induced by preconditioning, possibly by transcriptional activation of neuroprotective genes. Also, preconditioning enhances normalization of the disturbed cell signaling through the extracellular signal-regulated protein kinase cascade induced by lethal ischemia.</p>}},
  author       = {{Shamloo, M. and Rytter, A. and Wieloch, T.}},
  issn         = {{0306-4522}},
  keywords     = {{Brain ischemia; Cell death; Cell signaling; MAP kinase; Preconditioning; Tolerance}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{1}},
  pages        = {{81--88}},
  publisher    = {{Elsevier}},
  series       = {{Neuroscience}},
  title        = {{Activation of the extracellular signal-regulated protein kinase cascade in the hippocampal CA1 region in a rat model of global cerebral ischemic preconditioning}},
  url          = {{http://dx.doi.org/10.1016/S0306-4522(99)00137-2}},
  doi          = {{10.1016/S0306-4522(99)00137-2}},
  volume       = {{93}},
  year         = {{1999}},
}