Evidence for early induction of calmodulin gene expression in lymphocytes undergoing glucocorticoid-mediated apoptosis

Diane R. Dowd, Paul N. MacDonald, Barry S. Komm, Mark R Haussler, Roger Miesfeld

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Abstract

Glucocorticoid treatment of certain lymphoma cell lines and thymocytes activates a self-destructive pathway of programmed cell death referred to as apoptosis. Calcium and calmodulin (CaM) may be important signals in the apoptotic cascade because an early event is a sustained elevation in cytosolic Ca2+ and CaM inhibitors interfere with the death pathway. In the present study, expression of the CaM gene was examined during glucocorticoid-induced apoptosis in WEHI7.2 lymphocytes. Steady state levels of CaM mRNA were increased up to 10-fold following a 4-6-h exposure of WEHI7.2 cells to 10-6 M dexamethasone. This increase was mediated through the glucocorticoid receptor since the response was not observed in WEHI7.418, a variant line which does not express active glucocorticoid receptor. Induction of CaM mRNA was dose-dependent and highly specific for glucocorticoids, as other steroids were unable to elicit the response. A stringent cell specificity was also observed. Pretreatment of WEHI7.2 lymphocytes with cycloheximide did not interfere with dexamethasone-dependent increases in CaM mRNA levels, and studies with actinomycin D demonstrated that the stability of the transcript was not altered by hormone. Finally, a calmodulin inhibitor elicited a protective effect on WEHI7.2 cells following glucocorticoid exposure. These results indicate that CaM mRNA levels were hormonally controlled in WEHI7.2 lymphocytes and support the putative involvement of CaM in glucocorticoid-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)18423-18426
Number of pages4
JournalJournal of Biological Chemistry
Volume266
Issue number28
StatePublished - Oct 5 1991

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Lymphocytes
Calmodulin
Gene expression
Glucocorticoids
Apoptosis
Gene Expression
Messenger RNA
Glucocorticoid Receptors
Dexamethasone
Dactinomycin
Cell death
Thymocytes
Cycloheximide
Lymphoma
Cell Death
Genes
Steroids
Cells
Hormones
Calcium

ASJC Scopus subject areas

  • Biochemistry

Cite this

Evidence for early induction of calmodulin gene expression in lymphocytes undergoing glucocorticoid-mediated apoptosis. / Dowd, Diane R.; MacDonald, Paul N.; Komm, Barry S.; Haussler, Mark R; Miesfeld, Roger.

In: Journal of Biological Chemistry, Vol. 266, No. 28, 05.10.1991, p. 18423-18426.

Research output: Contribution to journalArticle

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