D609-mediated inhibition of ATP synthesis in neural progenitor cells

Neuroreport. 2014 Jul 9;25(10):777-81. doi: 10.1097/WNR.0000000000000176.

Abstract

Tricyclodecan-9-yl-xanthogenate (D609) is an antioxidative molecule with antiproliferative and neuroprotective properties in a variety of cells. Previously, we have shown that D609 decreased the proliferation of neural progenitor cells. In this study, we examined the antioxidative property of D609 on neural progenitor cells isolated from the subventricular zone of the rat brain. Cellular oxidation was assessed by measuring the ATP content of the cells. Our results show that D609 decreased the ATP content of the neural progenitor cells by ∼40%, suggesting the possible inhibition of cellular metabolic activity. Cytochrome c oxidase (Cox), also known as complex IV of the electron transport chain, is a terminal enzyme involved in the oxidation of substrates resulting in the generation of energy required for the cellular activity. Therefore, regulating the activity of Cox could interfere with the generation of ATP, consequently affecting the proliferation of cells. Consistent with this hypothesis, we also observed a decrease in the Cox activity following the incubation of neural progenitor cells with D609. These results suggest that D609 could inhibit the activity of Cox and subsequent ATP synthesis in the neural progenitor cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphate / biosynthesis*
  • Animals
  • Antioxidants / pharmacology*
  • Bridged-Ring Compounds / pharmacology*
  • Cells, Cultured
  • Electron Transport Complex IV / metabolism
  • Lateral Ventricles / drug effects
  • Lateral Ventricles / metabolism
  • Male
  • Mitochondria / drug effects
  • Neural Stem Cells / drug effects*
  • Neural Stem Cells / enzymology
  • Neural Stem Cells / metabolism*
  • Norbornanes
  • Rats
  • Rats, Inbred SHR
  • Thiocarbamates
  • Thiones / pharmacology*

Substances

  • Antioxidants
  • Bridged-Ring Compounds
  • Norbornanes
  • Thiocarbamates
  • Thiones
  • tricyclodecane-9-yl-xanthogenate
  • Adenosine Triphosphate
  • Electron Transport Complex IV