Investigation of the neuroprotective effects of a novel synthetic compound via the mitochondrial pathway

Abstract

The present study aimed to investigate the neuroprotective effect of a novel synthetic compound (5zou) on differentiated PC12 cells against 6-hydroxydopamine (6-OHDA) and L-glutamic acid (L-Glu) neurotoxin-induced cell injury and the potential mechanisms involved. 5zou is a 2, 2-disubstituted 1, 2-dihydropyridine. PC12 cells were treated with 6-OHDA and L-Glu to establish neurotoxic cell models. MTT assay, DCFH-DA staining, Fluo-4-AM staining, JC-1 staining and western blotting were used to determine the changes in cell viability, intracellular reactive oxygen species concentration, Ca2+ influx, mitochondrial membrane potential and the protein expressions of B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xL). Morphological analysis demonstrated the effect of 5zous on neuritogenesis and differentiation in PC12 cells. The results suggested that 5zou rescued the cell viability, intracellular ROS level, Ca2+ influx, mitochondrial membrane potential, and expression of Bcl-2 and Bcl-xL, which were altered by 6-OHDA and L-Glu. The study confirmed that 5zou has neuroprotective effects on neurotoxin-induced differentiated PC12 cells injury, potentially via the mitochondrial apoptosis pathway.