Augmented heme oxygenase-1 induces prostaglandin uptake via the prostaglandin transporter in micro-vascular endothelial cells

Michael L. Pucci, Bindu Chakkalakkal, Elvira L. Liclican, Alexander J. Leedom, Victor L. Schuster, Nader G. Abraham

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 ∼7-fold higher levels of PGT RNA and equivalently elevated uptake of [ 3H]PGE 2. The pattern and extent of uptake and the substrate inhibitory constants of PGE 2, PGF , 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.

Original languageEnglish (US)
Pages (from-to)1299-1305
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume323
Issue number4
DOIs
StatePublished - Oct 29 2004

Keywords

  • Endothelial cells
  • Heme oxygenase-1
  • Inflammation
  • Prostaglandin clearance
  • Prostaglandin transporter

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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