Everolimus Attenuates Glutamate-Induced PC12 Cells Death

سال انتشار: 1398
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 403

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شناسه ملی سند علمی:

NIMED03_119

تاریخ نمایه سازی: 7 آبان 1398

چکیده مقاله:

Glutamate-induced neuronal cell death plays a key role in neurodegenerative disorders such as Alzheimer’s disease. 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 mTORinhibitor. Therefore, the present study was designed to investigate whether EVR has protective effects against glutamate-induced neuronal injury and elucidate the underlying molecular mechanisms. Materials and Methods: PC12 cells were concurrently treated withEVR (0-40 nM) and glutamate (8 mM) for 24 h. Then, the cells viability, apoptosis rate, and proteins involved in apoptosis (caspase-3, bax and bcl-2) were measured using MTT, annexin V-PI and immunoblotting assays. Results: Analyzing the protective effect of differentconcentrations of EVR (0-40 nM) against glutamateinduced cytotoxicity revealed a significant increase in cell viability in co-treatment regimen (p<0.01). Also, EVR (40 nM) significantly (p<0.01) inhibited glutamateinduced apoptosis through depressing the elevation of bax/bcl-2 ratio and cleaved caspase-3 expression, in a concentration-dependent manner. Conclusion: The results demonstrated, for the first time, that EVR could protect against glutamate-mediated PC12 cell death via inhibiting apoptosis

نویسندگان

Mohaddeseh Sadat Alavi

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran

Sahar Fanoudi

Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Hamid Reza Sadeghnia

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran