Down-regulation of PTEN by sodium orthovanadate inhibits ASK1 activation via PI3-K/Akt during cerebral ischemia in rat hippocampus.

In this study, we examined the phosphorylation of ASK1, Akt and PTEN and the effects of sodium orthovanadate on these signal proteins during ischemia. Transient (15 min) brain ischemia was induced by the four-vessel occlusion in Sprague-Dawley rats. The following results were observed: (1) the decreased tyrosine phosphorylation of PTEN and the decreased serine phosphorylation of Akt induced by ischemia were suppressed by sodium orthovanadate, respectively. (2) The phosphorylation of ASK1 at serine 83 was decreased and the phosphorylation of ASK1 at threonine 845 was increased during ischemia. Sodium orthovanadate could alter the phosphorylation status of ASK1 at serine 83 and threonine 845 induced by ischemia. However, LY294002 could reverse the effect of sodium orthovanadate on the phosphorylation of ASK1 at threonine 845, namely, sodium orthovanadate inhibited ASK1 through the PI3-K/Akt-dependent pathway. Taken together, we concluded that sodium orthovanadate could increase the tyrosine posphorylation of PTEN and further inhibit the activation of ASK1 via activating Akt during cerebral ischemia.