Alterations of Akt1 (PKBalpha) and p70(S6K) in transient focal ischemia.
The serine-threonine kinase Akt1 promotes cell survival through inhibition of apoptosis. One of the potential downstream targets of Akt1 is p70 S6 kinase, p70(S6K), an enzyme implicated in the regulation of protein synthesis. In this study, we investigated the changes in total and phosphorylated levels of Akt1 and p70(S6K) during transient focal ischemia. Male Wistar rats were subjected to 2 h of middle cerebral artery occlusion followed by 1, 4, and 24 h of reperfusion. The expression of total and phosphorylated forms of Akt1 and p70(S6K) were examined by Western blot analysis. Phosphorylation of Akt1 on Ser473 transiently increased at 1 and 4 h of reperfusion, whereas phosphorylation of Akt1 on Thr308 was reduced during reperfusion. The levels of total Akt1 remained unchanged at 1 and 4 h of reperfusion, but decreased significantly at 24 h of reperfusion. Phosphorylation of p70(S6K) on Thr389 decreased at 1, 4, and 24 h of reperfusion, while the levels of total p70(S6K) protein remained unchanged at 1 and 4 h of reperfusion but decreased at 24 h of reperfusion. The results show that cell survival pathways, such as Akt1 and p70(S6K) signaling, are suppressed after transient focal ischemia, which may contribute to the development of neuronal cell death after an ischemic insult.
Janelidze
S
S
Center for the Study of Neurological Disease, The Queen's Neuroscience Institute, Honolulu, Hawaii, USA.
Hu
B R
BR
Siesjö
P
P
Siesjö
B K
BK
D000818:Animals; D029681:Arabidopsis Proteins; D015153:Blotting, Western; D003600:Cytosol / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D020768:Middle Cerebral Artery / Q000502:physiology; D010766:Phosphorylation; D010940:Plant Proteins / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*
D029681:Arabidopsis Proteins; D010940:Plant Proteins; D015221:Potassium Channels; C074500:AKT1 protein, Arabidopsis; D019893:Ribosomal Protein S6 Kinases