Methotrexate remediates spinal cord injury in vivo and in vitro via suppression of endoplasmic reticulum stress-induced apoptosis.

Methotrexate remediates spinal cord injury in vivo and in vitro via suppression of endoplasmic reticulum stress-induced apoptosis. Exp Ther Med. 2018 May;15(5):4191-4198 Authors: Rong F, Gao X, Liu K, Wu J Abstract It has been suggested that endoplasmic reticulum stress (ERS) may induce apoptosis following spinal cord injury (SCI). Methotrexate (MTX) has been used as a long-term therapy regimen for rheumatoid arthritis. However, it is not clear whether MTX remediates SCI by inhibiting ERS. In the present study, to establish an in vitro ERS cell model, PC12 cells were pre-incubated with triglycerides (TG). MTT assays revealed that treatment with 1, 2.5, 5 and 10 µM TG decreased PC12 cell viability in a dose-dependent manner. Additionally, MTX treatment significantly reversed the TG-induced decrease in cell viability and increased apoptosis according to the flow cytometry assay (P<0.05). Notably, western blotting indicated that MTX significantly decreased levels of glucose-regulated protein (GRP)78, CCAAT-enhancer-binding protein homologous protein (CHOP) and caspase-12 expression (P<0.05), which were increased following treatment with TG. Furthermore, the in vivo role of MTX in a rat model of SCI was evaluated. The motor behavioral function of rats was improved following treatment with MTX according to Basso, Beattie and Bresnahan scoring (P<0.05). Terminal deoxynucleotidyl-transferase-mediated dUTP nick end staining indicat...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research