Elevated glutathione S-transferase gene expression is an early event during steroid-induced lymphocyte apoptosis

Francis A. Flomerfelt, Margaret M Briehl, Diane R. Dowd, Ellen S. Dieken, Roger Miesfeld

Research output: Contribution to journalArticle

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Abstract

Based on the finding that glutathione S-transferase Yb1 (GST) gene expression is elevated in the regressing prostate of androgen-ablated rats, we analyzed GST transcript levels during steroid-induced lymphocyte cell death. It was found that GST gene expression was induced in steroid-sensitive cells within 4 hr of dexamethasone treatment, required functional glucocorticoid receptor, and was dose-dependent with regard to hormone. GST expression was not induced in an apoptosis-defective variant that contained normal levels of functional receptor, indicating that GST up-regulation was the result of secondary events that occur during steroid-mediated apoptosis. Using the calcium ionophore A23817 to induce lymphocyte cell death, GST RNA levels were increased in both steroidsensitive and steroid-resistant cell lines, supporting the conclusion that elevated GST expression was the result of cellular processes associated with apoptosis, rather than a direct consequence of steroid-mediated transcriptional control. The cells were also treated with dibutyryl cAMP to cause cell death; however, this mode of killing did not result in GST up-regulation. Taken together, these results suggest that GST induction in dexamethasone-treated T-lymphocytes occurs early in the steroid-regulated apoptotic pathway and that this may be a marker of calcium-stimulated cell death. Based on the known function of GST as an antioxidant defense enzyme and its transcriptional regulation by reactive oxygen intermediates, we propose that the gene product of a primary GR target gene(s) directly or indirectly effects the redox state of the cell. Thus activation of GST gene expression in apoptotic lymphocytes is likely a indicator of oxidative stress, rather than a required step in the pathway.

Original languageEnglish (US)
Pages (from-to)573-581
Number of pages9
JournalJournal of Cellular Physiology
Volume154
Issue number3
StatePublished - Mar 1993

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Lymphocytes
Glutathione Transferase
Gene expression
Steroids
Apoptosis
Gene Expression
Cell death
Cell Death
Dexamethasone
Up-Regulation
Genes
Oxidative stress
T-cells
Calcium Ionophores
Glucocorticoid Receptors
Androgens
Oxidation-Reduction
Rats
Prostate
Cause of Death

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Elevated glutathione S-transferase gene expression is an early event during steroid-induced lymphocyte apoptosis. / Flomerfelt, Francis A.; Briehl, Margaret M; Dowd, Diane R.; Dieken, Ellen S.; Miesfeld, Roger.

In: Journal of Cellular Physiology, Vol. 154, No. 3, 03.1993, p. 573-581.

Research output: Contribution to journalArticle

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