title: β1-Adrenergic receptor downregulates the expression of cyclooxygenase-2.
abstract: Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the generation of prostanoids, and is thus one of the key players in the inflammatory process. Contrary to the constitutively expressed isoform COX-1, the expression of COX-2 is rapidly and transiently upregulated following pathological stimuli but little is known about pathways that mediate its degradation. Here we show that co-expression of COX-2 together with the β1 adrenergic receptor (β1AR) specifically lowers the expression of COX-2 in a dose-dependent manner. We further find that stimulation of the receptor for prolonged periods of time does not reverse the β1AR-induced decrease in COX-2, suggesting that this effect does not occur via classical β1-mediated signaling pathways. Rather we find that the half-life of COX-2 is significantly decreased in the presence of β1AR and that inhibition of the proteasome reverses the effect of the receptor on COX-2. Together these findings ascribe a new role for β1AR in the downregulation of COX-2.
authors.affiliation: Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Mt. Carmel, Haifa 3498838, Israel.
authors.forename: Sivan
authors.initials: S
authors.lastname: Brender
authors.affiliation: Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Mt. Carmel, Haifa 3498838, Israel. Electronic address: lbarki@psy.haifa.ac.il.
authors.forename: Liza
authors.initials: L
authors.lastname: Barki-Harrington
mesh_terms: D058665:Adrenergic beta-1 Receptor Agonists / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004280:Dobutamine / Q000494:pharmacology; D015536:Down-Regulation; D004795:Enzyme Stability / Q000187:drug effects; D057809:HEK293 Cells; D006207:Half-Life; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D059748:Proteolysis / Q000187:drug effects; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D011500:Protein Synthesis Inhibitors; D018342:Receptors, Adrenergic, beta-1; D011994:Recombinant Proteins; D004280:Dobutamine; D003513:Cycloheximide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D046988:Proteasome Endopeptidase Complex
keywords: Cyclooxygenase-2; Degradation; β(1) adrenergic receptor