Document Detail


Hypoxic condition interferes with phosphorylation of Akt at Thr(308) in cultured rat pheochromocytoma-12 cells.
MedLine Citation:
PMID:  12399007     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phosphorylation of Akt induced under hypoxic or ischemic conditions has been reported only for residue Ser(473). We examined whether Akt can be phosphorylated at Thr(308), another phosphorylation site on Akt, and can exhibit neuroprotective effects under conditions of hypoxia/reoxygenation, comparing pheochromocytoma-12 (PC12) cells transfected with constitutively active Akt (Myr-pCMV cells) and those transfected with pCMV vector only (pCMV cells). Expression levels of Akt phosphorylated at Ser(473) were 2.1-fold higher in Myr-pCMV cells compared with pCMV cells, before the onset of hypoxia, which were increased transiently during hypoxia, and then decreased gradually during reoxygenation. In contrast, Akt phosphorylated at Thr(308) was not detected in pCMV cells under any conditions but was expressed in Myr-pCMV cells prior to hypoxia, followed by an immediate decrease during hypoxia and a further decline during reoxygenation. However, G1-arrest of the cell cycle observed at 12 h after hypoxia in pCMV cells was prevented in Myr-pCMV cells. These findings suggest that hypoxia activates Akt by phosphorylation at Ser(473) only, which is sufficient to elicit a neuroprotective function against hypoxic neuronal damage.
Authors:
Daiji Obara; Kimiaki Utsugisawa; Yuriko Nagane; Hideo Tohgi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuroscience letters     Volume:  332     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-10-25     Completed Date:  2003-02-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  167-70     Citation Subset:  IM    
Copyright Information:
Copyright 2002 Elsevier Science Ireland Ltd.
Affiliation:
Department of Neurology, Iwate Medical University, Uchimaru 19-1, Morioka 020-8505 Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia / metabolism*
Blotting, Western
Cytomegalovirus / genetics
DNA, Complementary / biosynthesis,  genetics
Genetic Vectors
Oncogene Protein v-akt
PC12 Cells
Phosphorylation
Rats
Retroviridae Proteins, Oncogenic / genetics,  metabolism*
Signal Transduction / physiology
Threonine / metabolism*
Tissue Fixation
Chemical
Reg. No./Substance:
0/DNA, Complementary; 0/Retroviridae Proteins, Oncogenic; 72-19-5/Threonine; EC 2.7.11.1/Oncogene Protein v-akt

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