Downregulation of the antioxidant defence during glucocorticoid-mediated apoptosis

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

Research output: Contribution to journalArticle

58 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

Fingerprint Dive into the research topics of 'Downregulation of the antioxidant defence during glucocorticoid-mediated apoptosis'. Together they form a unique fingerprint.

  • Cite this