کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10767934 | 1050801 | 2005 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Prostaglandin E2 induces cyclooxygenase-2 expression in human non-pigmented ciliary epithelial cells through activation of p38 and p42/44 mitogen-activated protein kinases
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Prostaglandins (PGs) have been implicated in lowering intraocular pressure (IOP). A possible role of cyclooxygenase-2 (COX-2) in this process was emphasized by findings showing impaired COX-2 expression in the non-pigmented ciliary epithelium (NPE) of patients with primary open-angle glaucoma. The present study investigates the effect of the major COX-2 product, PGE2, on the expression of its synthesizing enzyme in human NPE cells (ODM-2). PGE2 led to an increase of COX-2 mRNA and protein expression, whereas the expression of COX-1 remained unchanged. Upregulation of COX-2 expression by PGE2 was accompanied by time-dependent phosphorylations of p38 mitogen-activated protein kinase (MAPK) and p42/44 MAPK, and was abrogated by inhibitors of both pathways. Moreover, PGE2-induced COX-2 expression was suppressed by the intracellular calcium chelator, BAPTA/AM, and the protein kinase C inhibitor bisindolylmaleimide II, whereas the protein kinase A inhibitor H-89 was inactive in this respect. Induction of COX-2 expression was also elicited by butaprost (EP2 receptor agonist) and 11-deoxy PGE1 (EP2/EP4 receptor agonist), but not by EP1/EP3 receptor agonists (17-phenyl-Ï-trinor PGE2, sulprostone). Consistent with these findings, the EP1/EP2 receptor antagonist, AH-6809, and the selective EP4 receptor antagonist, ONO-AE3-208, significantly reduced PGE2-induced COX-2 expression. Collectively, our results demonstrate that PGE2 at physiologically relevant concentrations induces COX-2 expression in human NPE cells via activation of EP2- and EP4 receptors and phosphorylation of p38 and p42/44 MAPKs. Positive feedback regulation of COX-2 may contribute to the production of outflow-facilitating PGs and consequently to regulation of IOP.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 338, Issue 2, 16 December 2005, Pages 1171-1178
Journal: Biochemical and Biophysical Research Communications - Volume 338, Issue 2, 16 December 2005, Pages 1171-1178
نویسندگان
Susanne Rösch, Robert Ramer, Kay Brune, Burkhard Hinz,