Focal cerebral ischemia causes two temporal waves of Akt activation.
We studied whether pro-survival Akt was activated after transient focal cerebral ischemia and whether it inhibited pro-apoptotic Bad. Phosphorylation of Akt (serine-473) was enhanced in cortex after 1-hour ischemia, and also after 1h and 6 h of reperfusion, but it returned back to that in controls by 24 h. After this first wave of Akt activation, a second increase was observed between 4 and 7 days. In striatum, only the late Akt activation was seen. In contrast to Akt, no Bad phosphorylation (serine-136) was detected after ischemia. Therefore, injury spontaneously activated Akt, but this did not suppress Bad signalling. It is proposed that further pharmacological activation of Akt shortly after ischemia might promote cell survival, whereas Akt activation at longer time points is involved with glial reactivity.
Friguls
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B
Departament de Farmacologia i Toxicologia, Institut d'Investigacions Biomèdiques de Barcelona, CSIC-IDIBAPS, Rosselló, 161, planta 6, 08036 Barcelona, Spain.
Justicia
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C
Pallàs
M
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Planas
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AM
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002545:Brain Ischemia / Q000201:enzymology* / Q000503:physiopathology; D002352:Carrier Proteins / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology*; D002540:Cerebral Cortex / Q000201:enzymology* / Q000503:physiopathology; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000201:enzymology / Q000503:physiopathology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology* / Q000503:physiopathology; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D051025:bcl-Associated Death Protein
C494821:Bad protein, rat; D002352:Carrier Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D011518:Proto-Oncogene Proteins; D051025:bcl-Associated Death Protein; D012694:Serine; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt