Alterations of Akt1 (PKBα) and p70S6K in transient focal ischemia
Alterations of Akt1 (PKBα) and p70S6K in transient focal ischemia
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DOI：
10.1006/nbdi.2000.0325
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发表时间：
2001-02-01
影响因子：
6.1
通讯作者：
Siesjö, BK
中科院分区：
文献类型：
--
作者：
Janelidze, S;Hu, BR;Siesjö, BK
丝氨酸-苏氨酸激酶 Akt1 通过抑制细胞凋亡来促进细胞存活。 Akt1 的潜在下游靶标之一是 p70 S6 激酶，p70(S6K)，一种参与蛋白质合成调节的酶。在本研究中，我们研究了短暂局灶性缺血期间 Akt1 和 p70(S6K) 总水平和磷酸化水平的变化。雄性 Wistar 大鼠大脑中动脉闭塞 2 小时，然后再灌注 1、4 和 24 小时。通过蛋白质印迹分析检查 Akt1 和 p70(S6K) 的总和磷酸化形式的表达。 Akt1 在 Ser473 上的磷酸化在再灌注 1 和 4 小时时短暂增加，而 Akt1 在 Thr308 上的磷酸化在再灌注期间减少。再灌注1和4小时总Akt1水平保持不变，但再灌注24小时显着下降。 p70S6K在Thr389上的磷酸化在再灌注1、4和24小时时下降，而总p70(S6K)蛋白水平在再灌注1和4小时时保持不变，但在再灌注24小时时下降。结果表明，细胞存活途径，如 Akt1 和 p70(S6K) 信号传导，在短暂局灶性缺血后受到抑制，这可能有助于缺血性损伤后神经元细胞死亡的发展。,(C) 2001 学术出版社。
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 p70S6K 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.,(C) 2001 Academic Press.