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

Minaei Beyrami, Sohrab and Khadem Ansari, Mohammad Hasan and Rasemi, Yousef and Shakib, Nader and Karimi, Pouran (2018) Complete inhibition of phosphatase and tensin homolog promotes the normal and oxygen-glucose deprivation/reperfusion-injured PC12 cells to cell death. Journal of Cardiovascular and Thoracic Research, 10 (2). pp. 83-89. ISSN 2008-5117

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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.

Item Type: Article
Subjects: Science Global Plos > Medical Science
Depositing User: Unnamed user with email support@science.globalplos.com
Date Deposited: 03 May 2023 07:52
Last Modified: 12 Jan 2024 07:15
URI: http://ebooks.manu2sent.com/id/eprint/736

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