The Neuroprotective Role of Nimodipine and nNOS Inhibitor Against Bortezomib-Induced Cell Death in Schwann Cells

Nova Southeastern University, Davie, Florida, USA

Objective. The study was conducted to assess the neuroprotective role of Nimodipine (Nim) and nNOS inhibitor (nNi) against bortezomib (BTZ)-induced cell death in Schwann cells (RT4-D6P2T). Background. Schwann cells (SC) are myelinating cells, known to maintain the integrity and regeneration of neurons in the peripheral nervous system (PNS). Our study was designed to determine the molecular mechanisms involved in the use of neuroprotective agents against bortezomib-induced damage in SC. Methods. In our study, the cell viability of BTZ-treated cells was measured after 24, 48, and 72 h of treatments, followed by neuroprotective studies with Nim and nNi. Reactive oxygen species (ROS) and mitochondrial membrane potential (Δψm) were assessed using DCFDA and JC-1 staining method. Western blot analysis was conducted for measuring phospho-epidermal growth factor receptor (pEGFR), myelin basic protein (MBP), Protein kinase B (AKT) and phospho-Protein kinase B (pAKT) protein levels. Results. BTZ (1 µM) treatment was able to significantly reduce the cell viability after 24 h treatment compared to untreated controls. In addition, pre-treatment with Nim (10 µM) and nNi (1 µM) demonstrated significant upregulation of pAKT levels in BTZ-treated cells, while a significant decrease in MBP expression levels was observed. Interestingly, marginal decrease was observed in Nim and nNi pre-treated cells. Conclusion. Our results indicate that the neuroprotective role of Nim and nNi may be due to upregulation of pAKT and related pathways. Grants. This study was funded by the PFRDG grant 334818 and the financial support from the Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida.