title: Regulation of the expression of cyclooxygenases and production of prostaglandin I₂ and E₂ in human coronary artery endothelial cells by curcumin.
abstract: Curcumin regulates prostaglandin (PG) synthesis in a variety of cells. PGE₂ and PGI₂ are generated from arachidonic acid (AA) by cyclooxygenases 1 and 2 (COX-1 and COX-2) and the synthase (PGES and PGI₂S) pathways. This study evaluates the in vitro effect of curcumin on the expression of COX-1, COX-2, PGI₂S and microsomal PGES-1 (mPGES-1), and the production of PGE₂ and PGI₂ in human coronary artery endothelial cells (HCAEC). HCAEC monolayers were incubated with curcumin and the expression of mRNA, protein and the production of PGI₂ and PGE₂ were quantified. Incubation of HCAEC with curcumin led to a time and concentration-dependent increases in COX-2 mRNA with a small but significant decrease in COX-1 mRNA expression. Curcumin also stimulated the expression of PGI₂S and mPGES-1 mRNA. Although curcumin stimulated COX-2, PGI₂S and mPGES-1 gene expression, it failed to increase PGI₂ or PGE₂ production. Interestingly, supplementation of the culture medium with AA increased prostanoid production by both quiescent and curcumin-treated cells. However, in comparison to the quiescent cells, the prostanoid production by curcumin-treated cells was markedly enhanced as AA concentrations in the medium were increased, and the enhanced prostanoid production was blocked by the presence of COX-2 specific inhibitor. Taken together, these results suggest that curcumin regulates prostanoid homeostasis in HCAEC by modulating multiple steps including the expression of COX-1, COX-2, PGI₂S and mPGES-1.
authors: Division of Allergy, Clinical Immunology and Rheumatology, Department of Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
authors: X
authors: X
authors: Tan
authors: E M
authors: EM
authors: Poulose
authors: V V
authors: VV
authors: Raveendran
authors: B-T
authors: BT
authors: Zhu
authors: D J
authors: DJ
authors: Stechschulte
authors: K N
authors: KN
authors: Dileepan
mesh_terms: D016718:Arachidonic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003474:Curcumin / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000071876:Prostaglandin-E Synthases
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; C022461:prostacyclin synthetase; D003474:Curcumin; D015232:Dinoprostone