Everolimus attenuates glutamate-induced PC12 cells death.

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\u2009mM) and EVR (0-40\u2009nM) for 24\u2009h. 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\u2009nM) against glutamate-induced cytotoxicity revealed a significant increase in cell viability in co-treatment regimen (p\u2009<\u20090.01). Also, EVR (40\u2009nM) significantly (p\u2009<\u20090.01) 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.