Upregulation of Akt phosphorylation at the early stage of middle cerebral artery occlusion in mice

Mamoru Shibata, Takemori Yamawaki, Takahiro Sasaki, Hidenori Hattori, Junichi Hamada, Yasuo Fukuuchi, Hideyuki Okano, Masayuki Miura

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60 Citations (Scopus)

Abstract

Akt is a serine/threonine kinase that is believed to promote cell viability in many different cell types, including neurons. Here, we observed the state of Akt phosphorylation at several time points (1, 3, 6, 12, and 24 h) during permanent occlusion of the middle cerebral artery (MCA) in mice. We detected a transient upregulation of Akt phosphorylation at 1 h of MCA occlusion (MCAO) by Western blot analysis. Double immunostaining revealed that the enhanced phosphorylation of Akt occurred mainly in neurons located in the outer area of the MCA territory (ischemic penumbra). This phenomenon was accompanied by the nuclear translocation of Akt. We confirmed that Akt enzymatic activity is elevated in both the nuclear and cytosolic fractions of brain tissue subjected to 1 h of ischemia. cAMP-response-element-binding protein (CREB), an intranuclear target molecule of Akt, exhibited increased phosphorylation after 1 h of MCAO. In our ischemia model, caspase-3 was activated in the central part of the MCA territory as little as 1 h after MCAO. However, caspase-3 activation was not recognized at this time in the outer area of the MCA territory, where Akt activity was upregulated. These results suggest that prosurvival cell signaling is initiated in an active fashion before cell death pathways are activated in neurons situated in the ischemic penumbra at the early stage of ischemia.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalBrain Research
Volume942
Issue number1-2
DOIs
Publication statusPublished - 2002 Jun 28

Keywords

  • Akt (protein kinase B)
  • CAMP-response-element-binding protein (CREB)
  • Caspase
  • Cerebral ischemia
  • Ischemic penumbra
  • PTEN

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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  • Cite this

    Shibata, M., Yamawaki, T., Sasaki, T., Hattori, H., Hamada, J., Fukuuchi, Y., Okano, H., & Miura, M. (2002). Upregulation of Akt phosphorylation at the early stage of middle cerebral artery occlusion in mice. Brain Research, 942(1-2), 1-10. https://doi.org/10.1016/S0006-8993(02)02474-5