Complete inhibition of phosphatase and tensin homolog promotes the normal and oxygen-glucose deprivation/reperfusion-injured PC12 cells to cell death

Lipid phosphatase and tensin homolog deleted from chromosome 10 (PTEN) antagonizes phosphoinositide 3-kinase (PI3K)/AKT cell survival pathway. The effect of PTEN inhibitors has been rarely examined on cell survival following reperfusion injury. In this study, we investigated the neuroprotective effect of SF1670, as a new PTEN inhibitor, on an in vitro stroke-like model.
PC12 cells were exposed to oxygen-glucose deprivation/reperfusion (OGD/R). The cells were treated in five conditions as follows: normoxic normoglycemic (NO/NG); 60 minutes OGD; 60 minutes OGD and 6 h reperfusion (OGD/R); OGD/R treated with 10 µM SF1670 (OGD/R-SF), and NO/NG treated with 10 µM SF1670 (NO/NG-SF). Then, phosphorylation levels of AKT, P38 in PC12 cells were measured by immunoblotting. The cell viability was also determined by colorimetric assay.
The results of immunoblotting revealed that following OGD/R the levels of phospho-AKT (p-AKT) significantly decreased, compared to NO/NG cells (P Overall, our results demonstrated that complete inhibition of phosphatase activity of PTEN not only did not exhibit neuroprotective effect but also promoted PC12-deprived cells to death.