Arachidonic acid converts the glutathione depletion-induced apoptosis to necrosis by promoting lipid peroxidation and reducing caspase-3 activity in rat glioma cells

Arch Biochem Biophys. 2002 Apr 1;400(1):133-40. doi: 10.1006/abbi.2002.2784.

Abstract

Intracellular glutathione (GSH) depletion induced by buthionine sulfoximine (BSO) caused cell death that seemed to be apoptosis in C6 rat glioma cells. Arachidonic acid (AA) promoted BSO-induced cell death by accumulating reactive oxygen species (ROS) or hydroperoxides. AA inhibited caspase-3 activation and internucleosomal DNA fragmentation during the BSO-induced GSH depletion. Furthermore, AA reduced intracellular ATP content, induced dysfunction of mitochondrial membrane and enhanced 8-hydroxy-2'-deoxyguanosine (8-OH-dG) production. There was significant increase of 12-lipoxygenase activity in the presence of AA under the BSO-induced GSH depletion in C6 cells. These results suggest that AA promotes cell death by changing to necrosis from apoptosis through lipid peroxidation initiated by lipid hydroperoxides produced by 12-lipoxygenase under the GSH depletion in C6 cells. Some ROS such as hydroperoxide produced by unknown pathway make hydroxy radicals and induce 8-OH-dG formation in the cells. The conversion of apoptosis to necrosis may be a possible event under GSH depleted conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Apoptosis*
  • Arachidonate 12-Lipoxygenase / metabolism
  • Arachidonic Acid / metabolism*
  • Blotting, Western
  • Caspase 3
  • Caspases / metabolism*
  • Cell Death
  • Cell Line
  • DNA Fragmentation
  • Dose-Response Relationship, Drug
  • Electrophoresis, Agar Gel
  • Enzyme Activation
  • Glioma / enzymology*
  • Glioma / metabolism
  • Glutathione / metabolism*
  • Lipid Metabolism
  • Lipid Peroxidation
  • Membrane Potentials
  • Necrosis
  • Oxygen / metabolism
  • Rats
  • Reactive Oxygen Species
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Reactive Oxygen Species
  • Arachidonic Acid
  • Adenosine Triphosphate
  • Arachidonate 12-Lipoxygenase
  • Casp3 protein, rat
  • Caspase 3
  • Caspases
  • Glutathione
  • Oxygen