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

Introduction: 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. methods: 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/rsf), 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. results: the results of immunoblotting revealed that following ogd/r the levels of phospho- akt (p-akt) significantly decreased, compared to no/ng cells (p < 0.05). however, the ratio of p-akt/total akt significantly increased in the presence of sf1670 in the ogd/r-sf group, compared to the ogd/r condition. on the other hand, sf1670 significantly reduced the p-p38 mapk and p-jnk levels, compared to ogd/r cells. moreover, cell viability significantly decreased in the ogd and ogd/r condition compared to no/ng cells. surprisingly, sf-treated cells (ogd/r-sf and no/ng-sf group) showed low cell viability compared to no/ng condition. conclusion: 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.