Sa. Wajemanchao et al., MECHANISM OF CATECHOLAMINE-MEDIATED DESTABILIZATION OF MESSENGER-RNA ENCODING THY-1 PROTEIN IN T-LINEAGE CELLS, The Journal of immunology (1950), 161(9), 1998, pp. 4825-4833
The Ig superfamily cell surface glycoprotein Thy-1 expressed on immune
cells and neurons of rodents and humans is hypothesized to function i
n cell adhesion and signal transduction in T cell differentiation, pro
liferation, and apoptosis, This study analyzes effects of cAMP and cat
echolamines on transcriptional Thy-1 gene expression, Incubation of mu
rine thymocytes or S49 mouse thymoma cells with dibutyryl-cAMP, 8-brom
o-cAMP, cholera toxin, norepinephrine, or isoproterenol caused time- a
nd concentration-dependent decreases in levels of Thy-1 mRNA assayed b
y Northern hybridization or T2 nuclease protection, After 4 h of treat
ment with 500 mu M dibutyryl-cAMP or 8-bromo-cAMP, 1 nM cholera toxin,
100 mu M norepinephrine, or 100 mu M isoproterenol, Thy-1 mRNA levels
were 60 to 96% lower than those of controls, Norepinephrine-mediated
decreases in Thy-1 mRNA levels were prevented by the beta-adrenergic r
eceptor antagonist propranolol (10 mu M) Dibutyryl-cAMP and norepineph
rine decreased the apparent half-life of S49 cell Thy-1 mRNA from >>6
h to 2 to 3 h, whereas nuclear run-on assays showed no cAMP or norepin
ephrine effect on de novo transcription of the Thy-1 gene. In mutant S
49 cells lacking cAMP-dependent protein kinase A, neither dibutyryl cA
MP nor norepinephrine affected Thy-1 mRNA levels. These observations s
how that exogenous cAMP and norepinephrine can induce decreases in ste
ady state Thy-1 mRNA levels in T-lineage cells through posttranscripti
onal destabilization of Thy-1 mRNA, associated with protein kinase A-m
ediated protein phosphorylation. Catecholamine-mediated beta-adrenergi
c protein kinase A-dependent Thy-1 mRNA destabilization may be an exam
ple of a more general mRNA decay system regulating cellular responses
to stress.