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Κυριακή 5 Σεπτεμβρίου 2021

Rosuvastatin protects PC12 cells from hypoxia/reoxygenation-induced injury by inhibiting endoplasmic reticulum stress-induced apoptosis

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Exp Ther Med. 2021 Oct;22(4):1189. doi: 10.3892/etm.2021.10623. Epub 2021 Aug 17.

ABSTRACT

The endoplasmic reticulum stress (ERS) response serves an important role in cerebral ischemia-reperfusion injury (CIRI). However, to the best of the our knowledge, the effect of rosuvastatin on the ERS response in CIRI has not yet been studied. In the present study, the effect of rosuvastatin on cell damage in CIRI was investigated; furthermore, the effect of rosuvastatin on the ERS response was explored. Firstly, a hypoxia/reoxygenation (H/R)-induced cell damage model was established in PC12 cells. Cell viability was subsequently detected by a Cell Counting Kit-8 assay. A lactate dehydrogenase kit was used to detect cytotoxicity. TUNEL assay was then used to measure the extent of cell apoptosis, and western blotting was used to analyze the expression levels of the apoptosis-associated proteins Bax, Bcl-2, cleaved caspase-3 and cleaved caspase-9. In addition, western blotting was used to detect the expression levels of ERS-associated proteins, including phosphorylated (p)-protein kinase R-like endoplasmic reticulum kinase (PERK), p-eukaryotic initiation factor 2α and other proteins. Treatment with rosuvastatin led to an increased activity of H/R-induced PC12 cells and a decrease in their cytotoxicity. Rosuvastatin also led to an inhibition in apoptosis and ERS in H/R-induced PC12 cells. After administration of the ERS response activator thapsigargin (TG), TG was found to reverse the protective effect of rosuvastatin on injury of H/R-induced PC12 cells. Taken together, these findings have shown that rosuvastatin is able to protect PC12 cells from H/R-induced injury via inhibiting ERS-induced apoptosis, providing a strong theoretical basis for the use of rosuvastatin in the clinical treatment of CIRI.

PMID:34475979 | PMC:PMC8406900 | DOI:10.3892/etm.2021.10623

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