Everolimus attenuates glutamate-induced PC12 cells death. (3rd April 2023)

• Record Type: Journal Article
• Authors: Alavi, Mohaddeseh Sadat; Fanoudi, Sahar; Hosseini, Azar; Jalili-Nik, Mohammad; Bagheri, Amirbehzad; Sadeghnia, Hamid R.
• Is Part Of: International journal of neuroscience. Volume 133:Number 4(2023)
• Page Start: 457
• Page End: 466
• Publication Date: 2023-04-03
• Subjects: Everolimus -- apoptosis -- cytotoxicity -- glutamate -- mTOR -- PC12 cells; Nervous system -- Periodicals; 612.805
• DOI: 10.1080/00207454.2021.1929210
• Languages: English
• ISSNs: 0020-7454

Abstract

Abstract: Background: Glutamate-induced neuronal cell death plays a key role in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Some recent studies reported the potential immunomodulatory and neuroprotective properties of inhibitors of serine-threonine kinase, mTOR (mammalian target of rapamycin). However, no study was conducted about the neuroprotective potential of everolimus (EVR), a selective and potent mTOR inhibitor. Therefore, this study was planned to investigate whether EVR has protective effects against glutamate-induced toxicity in PC12 cells, which are used as model for neurons injury, and to elucidate the underlying mechanism. Methods: PC12 cells were concurrently treated with glutamate (8 mM) and EVR (0-40 nM) for 24 h. Then, the cells viability, apoptosis rate, and apoptosis-related proteins (caspase-3, bax and bcl-2) were measured using MTT, annexin V/PI and immunoblotting assays. Results: Analyzing the protective effect of different concentrations of EVR (0-40 nM) against glutamate-induced cytotoxicity revealed a significant increase in cell viability in co-treatment regimen ( p < 0.01). Also, EVR (40 nM) significantly ( p < 0.01) inhibited glutamate-induced apoptosis through depressing the elevation of bax/bcl-2 ratio and expression of cleaved caspase-3, concentration depend. Conclusion: The results demonstrated, for the first time, that EVR could protect against glutamate-mediated PC12 cell death via inhibiting apoptosis.