Mar 4, 1996

Cellular responses of cultured cerebellar astrocytes to ethacrynic acid-induced perturbation of subcellular glutathione homeostasis

Brain Research
J Huang, Martin A Philbert

Abstract

Glutathione (GSH) and glutathione-related enzyme systems in astrocytes play an important role in cellular defense against oxidative stress in the nervous system. The present study was designed to characterize the cellular responses of cultured astrocytes to chemically-induced perturbations of mitochondrial and cytosolic GSH homeostasis. Treatment of astrocytes in culture with ethacrynic acid (EA), a mitochondrion-penetrating thiol reagent, induced rapid and extensive depletion of both cytosolic and mitochondrial pools of GSH. Concomitant with the effects of EA on cellular GSH were significant and concentration-dependent increases in intracellular generation of reactive oxygen species (ROS) as indicated by the oxidation of preloaded 2',7'-dichlorofluorescein diacetate. Significant elevation of intracellular ROS occurred by 15 min following exposure to 100 microM EA and reached peak levels by 30 min which were approximately 7-fold higher than corresponding control levels. Ethacrynic acid-induced GSH depletion and intracellular ROS elevation was followed by marked decreases in glutathione reductase (GR) activity in mitochondria, and to a lesser extent, in cytosolic fractions of cultured astrocytes. This inhibitory effect was time-...Continue Reading

  • References18
  • Citations49
  • References18
  • Citations49

Citations

Mentioned in this Paper

Glucocorticoid-remediable Aldosteronism
Noncompetitive Inhibition
Enzymes, antithrombotic
Diacetyldichlorofluorescein
Rhodamine 123
Extravasation
Energy Metabolism
Protoplasm
Entire Nervous System
GAPDH gene

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