Augmented heme oxygenase-1 induces prostaglandin uptake via the prostaglandin transporter in micro-vascular endothelial cells |
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Authors: | Pucci Michael L Chakkalakkal Bindu Liclican Elvira L Leedom Alexander J Schuster Victor L Abraham Nader G |
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Institution: | Department of Pharmacology, New York Medical College, Valhalla, NY, USA. michael_pucci@nymc.edu |
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Abstract: | Previous studies show that expression of heme oxygenase-1 (HO-1) in endothelial cells results in decreased cyclooxygenase expression and prostaglandin (PG) levels through limiting heme availability. Regulation of PGs, important inflammatory mediators, may contribute to the anti-inflammatory potential of HO-1. Here we examine the effects of HO-1 expression on PG clearance via the prostaglandin transporter (PGT). Endothelial cells expressing human HO-1 via retroviral transfer exhibit approximately 7-fold higher levels of PGT RNA and equivalently elevated uptake of (3)H]PGE(2). The pattern and extent of uptake and the substrate inhibitory constants of PGE(2), PGF(2alpha), and thromboxane B(2) are similar to those of cloned PGT. Treatment of cells with stannous chloride, an inducer of HO-1, results in increased expression of PGT while incubation of cells expressing human HO-1 with stannic mesophorphyrin, a substrate inhibitor of HO-1, decreases PG uptake. Therefore, PG clearance via PGT may contribute to the cellular regulation of PG levels by HO-1. |
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Keywords: | Prostaglandin transporter Heme oxygenase-1 Endothelial cells Inflammation Prostaglandin clearance |
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