Submitted: 18 Feb 2017
Revised: 11 Apr 2018
Accepted: 26 Apr 2018
First published online: 21 May 2018
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J Cardiovasc Thorac Res. 2018;10(2):83-89.
doi: 10.15171/jcvtr.2018.13
  Abstract View: 134
  PDF Download: 261

Original Article

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

Abstract

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/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.
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.
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