Downregulation of the antioxidant defence during glucocorticoid-mediated apoptosis

Margaret M. Briehl, Ian A. Cotgreave, Garth Powis

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Recent studies implicate oxidative stress in the mechanism of apoptosis. We have examined the expression of genes, whose products counteract oxidative stress, during glucocorticoid-mediated apoptosis of a murine thymoma-derived cell line. Using Northern blot hybridisation analyses, we observed a progressive decline over a 24 h period in the transcript levels for catalase, manganese Superoxide dismutase, copper, zinc-superoxide dismutase, DT-diaphorase and thioredoxin. The changes were first seen within 2-8 h of the addition of the hormone which is well in advance of appreciable apoptosis. Using Western blot hybridisation analyses we found that a dexamethasone-mediated increase in glutathione S-transferase message level was followed closely by an increase in glutathione S-transferase mu class protein and a 20% decrease in reduced glutathione levels. Our findings suggest that the downregulation of cellular oxidant defense enzymes with a consequent increase in oxidant damage could contribute to the molecular mechanism of apoptosis.

Original languageEnglish (US)
Pages (from-to)41-46
Number of pages6
JournalCell Death and Differentiation
Volume2
Issue number1
StatePublished - Dec 1 1995

Keywords

  • Apoptosis
  • Gene expression
  • Glutathione S-transferase
  • Lymphocytes
  • Oxidative stress
  • Steroid hormones

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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