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

Mol Med Rep. 2017 Aug;16(2):1133-1138. doi: 10.3892/mmr.2017.6745. Epub 2017 Jun 9.

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.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cell Differentiation / drug effects
  • Cell Nucleus Shape / drug effects
  • Cell Survival / drug effects
  • Glutamic Acid
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Neurotoxins / toxicity
  • Oxidopamine
  • PC12 Cells
  • Rats
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*
  • bcl-X Protein / metabolism

Substances

  • Neuroprotective Agents
  • Neurotoxins
  • Reactive Oxygen Species
  • bcl-X Protein
  • Glutamic Acid
  • Oxidopamine
  • Calcium