Thioredoxin reductase and glutathione synthesis is upregulated by t-butylhydroquinone in cortical astrocytes but not in cortical neurons

Glia. 2000 Sep;31(3):241-8. doi: 10.1002/1098-1136(200009)31:3<241::aid-glia50>;2-9.


The electron donors glutathione and thioredoxin play many vital roles in the mechanisms of cells to cope with oxidative stress. Critical to such antioxidant functions are the ability to synthesize glutathione and keep it reduced via glutathione reductase and the ability to reduce oxidized-thioredoxin via thioredoxin reductase. The rate-limiting enzyme for glutathione synthesis, gamma-glutamylcysteine synthase, is regulated by the antioxidant response element, whereas little is known about the regulation of expression of the selenoenzyme thioredoxin reductase. There were several objectives in this study. One was to determine whether the phase II enzyme inducer t-butylhydroquinone would increase thioredoxin reductase in neural cells; we found that both cytosolic and mitochondrial thioredoxin reductase activity and protein content is increased in cortical astrocytes, but not in cortical neurons. A second objective was to determine whether there are differences in the ability of t-butylhydroquinone to increase glutathione content in astrocytes and neurons; we found that glutathione is increased in astrocytes but not neurons. Finally, t-butylhydroquinone addition did not affect glutathione reductase activity in neurons and caused only a modest increase in astrocytes. Our findings emphasize the central role that astrocytes play in the antioxidant activities of the CNS. Our findings also suggest that thioredoxin reductase and gamma-glutamylcysteine synthase belong to the same synexpression group.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Astrocytes / cytology
  • Astrocytes / drug effects*
  • Astrocytes / enzymology
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / enzymology
  • Glutathione / biosynthesis
  • Glutathione / drug effects*
  • Hydroquinones / metabolism
  • Hydroquinones / pharmacology*
  • Mice
  • Mice, Inbred Strains
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Subcellular Fractions
  • Thioredoxin-Disulfide Reductase / drug effects*
  • Thioredoxin-Disulfide Reductase / metabolism


  • Antioxidants
  • Hydroquinones
  • 2-tert-butylhydroquinone
  • Thioredoxin-Disulfide Reductase
  • Glutathione