Cyclic AMP potentiates glucocorticoid-induced endogenous endonuclease activation in thymocytes

David McConkey, Sten Orrenius, Sam Okret, Mikael Jondal

Research output: Contribution to journalArticle

Abstract

The present study was undertaken to determine whether specific interactions between cAMP and glucocorticoids regulate apoptosis in thymocytes. Incuba-tion of murine thymocytes with agents that elevate the cAMP level resulted in enhancement of glucocorticoid-induced Ca2+ increases, DNA fragmentation, and cell death compared to levels observed in thymocytes treated with steroid alone. cAMP did not affect DNA fragmentation in thymocytes treated with Ca2+ ionophore, a compound that induces endonuclease activation via an independent mechanism. Treatment with cAMP also increased glucocorticoid potency by lowering the concentration of steroid required for induction of apoptosis. The mechanism of cAMP action appeared to involve the glucocorticoid receptor, since the glucocorticoid antagonist RU-486 abrogated the cAMP response in animals treated with the adenosine analog NECA in vivo. Analysis of cellular glucocorticoid binding and receptor protein levels revealed modest cAMP-stimulated increases that appeared insufficient to account for the effects of cAMP on endogenous endonuclease activation, suggesting the possible involvement of a posttranslational mechanism in the response. These results demonstrate that cAMP and glucocorticoids synergize to promote apoptosis in thymocytes via a mechanism that appears to involve modification of glucocorticoid receptor activity.

Original languageEnglish (US)
Pages (from-to)580-585
Number of pages6
JournalFASEB Journal
Volume7
Issue number6
StatePublished - Apr 1 1993
Externally publishedYes

Fingerprint

thymocytes
Endonucleases
cyclic AMP
Thymocytes
glucocorticoids
Cyclic AMP
Glucocorticoids
Chemical activation
Glucocorticoid Receptors
DNA Fragmentation
Apoptosis
apoptosis
DNA fragmentation
steroids
Steroids
Adenosine-5'-(N-ethylcarboxamide)
Mifepristone
Ionophores
calcium
Adenosine

Keywords

  • Apoptosis
  • Calcium
  • Glucocorticoid receptor
  • Programmed cell death

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Cyclic AMP potentiates glucocorticoid-induced endogenous endonuclease activation in thymocytes. / McConkey, David; Orrenius, Sten; Okret, Sam; Jondal, Mikael.

In: FASEB Journal, Vol. 7, No. 6, 01.04.1993, p. 580-585.

Research output: Contribution to journalArticle

McConkey, David ; Orrenius, Sten ; Okret, Sam ; Jondal, Mikael. / Cyclic AMP potentiates glucocorticoid-induced endogenous endonuclease activation in thymocytes. In: FASEB Journal. 1993 ; Vol. 7, No. 6. pp. 580-585.
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