Mechanism of catecholamine-mediated destabilization of messenger RNA encoding Thy-1 protein in T-lineage cells.
The Ig superfamily cell surface glycoprotein Thy-1 expressed on immune cells and neurons of rodents and humans is hypothesized to function in cell adhesion and signal transduction in T cell differentiation, proliferation, and apoptosis. This study analyzes effects of cAMP and catecholamines on transcriptional Thy-1 gene expression. Incubation of murine thymocytes or S49 mouse thymoma cells with dibutyryl-cAMP, 8-bromo-cAMP, cholera toxin, norepinephrine, or isoproterenol caused time- and concentration-dependent decreases in levels of Thy-1 mRNA assayed by Northern hybridization or T2 nuclease protection. After 4 h of treatment with 500 microM dibutyryl-cAMP or 8-bromo-cAMP, 1 nM cholera toxin, 100 microM norepinephrine, or 100 microM 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 receptor antagonist propranolol (10 microM). Dibutyryl-cAMP and norepinephrine 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 norepinephrine effect on de novo transcription of the Thy-1 gene. In mutant S49 cells lacking cAMP-dependent protein kinase A, neither dibutyryl cAMP nor norepinephrine affected Thy-1 mRNA levels. These observations show that exogenous cAMP and norepinephrine can induce decreases in steady state Thy-1 mRNA levels in T-lineage cells through posttranscriptional destabilization of Thy-1 mRNA, associated with protein kinase A-mediated protein phosphorylation. Catecholamine-mediated beta-adrenergic protein kinase A-dependent Thy-1 mRNA destabilization may be an example of a more general mRNA decay system regulating cellular responses to stress.
Wajeman-Chao
S A
SA
Department of Biochemistry and Molecular Biology, University of Illinois, Chicago 60612-7334, USA.
Lancaster
S A
SA
Graf
L H
LH
Chambers
D A
DA
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D019070:Cell Lineage; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006207:Half-Life; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009638:Norepinephrine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D018800:Thy-1 Antigens / Q000096:biosynthesis / Q000235:genetics*; D013945:Thymoma / Q000473:pathology; D013950:Thymus Gland / Q000166:cytology; D013953:Thymus Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D018800:Thy-1 Antigens; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D002772:Cholera Toxin; D011433:Propranolol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol; D009638:Norepinephrine