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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Fernández-martínez, Ana B. Arenas Jiménez, María I. Lucio Cazaña, Francisco J. |
| Description | Author Affiliation: Fernández-Martínez AB ( Departamento de Fisiología, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain. anab.fernandez@uah.es) |
| Abstract | We have previously shown in HK-2 cells that ATRA (all-trans-retinoic acid) up-regulates HIF-1α (hypoxia-inducible factor-1α) in normoxia, which results in increased production of renal protector VEGF-A (vascular endothelial growth factor-A). Here we investigated the role of COXs (cyclooxygenases) in these effects and we found that, i) ATRA increased the expression of COX-1 and COX-2 mRNA and protein and the intracellular levels (but not the extracellular ones) of $PGE_{2}.$ Furthermore, inhibitors of COX isoenzymes blocked ATRA-induced increase in intracellular $PGE_{2},$ HIF-1α up-regulation and increased VEGF-A production. Immunofluorescence analysis found intracellular staining for EP1-4 receptors $(PGE_{2}$ receptors). These results indicated that COX activity is critical for ATRA-induced HIF-1α up-regulation and suggested that intracellular $PGE_{2}$ could mediate the effects of ATRA; ii) Treatment with $PGE_{2}$ analog $16,16-dimethyl-PGE_{2}$ resulted in up-regulation of HIF-1α and antagonists of EP1-4 receptors inhibited $16,16-dimethyl-PGE_{2}-$ and ATRA-induced HIF-1α up-regulation. These results confirmed that $PGE_{2}$ mediates the effects of ATRA on HIF-1α expression; iii) Prostaglandin uptake transporter inhibitor bromocresol green blocked the increase in HIF-1α expression induced by $PGE_{2}$ or by $PGE_{2}-increasing$ cytokine interleukin-1β, but not by ATRA. Therefore only intracellular $PGE_{2}$ is able to increase HIF-1α expression. In conclusion, intracellular $PGE_{2}$ increases HIF-1α expression and mediates ATRA-induced HIF-1α up-regulation. |
| ISSN | 00063002 |
| Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number | 4 |
| Volume Number | 1821 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2012-04-01 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | Dinoprostone Metabolism Hypoxia-Inducible Factor 1, Alpha Subunit Kidney Tubules, Proximal Drug Effects Signal Transduction Tretinoin Pharmacology Blotting, Western Cell Hypoxia Cell Line Cell Line, Tumor Cyclooxygenase 1 Genetics Cyclooxygenase 2 Cyclooxygenase Inhibitors Interleukin-1beta Intracellular Space Cytology Pyrazoles Reverse Transcriptase Polymerase Chain Reaction Sulfonamides Up-Regulation Vascular Endothelial Growth Factor A Research Support, Non-U.S. Gov't Biochemistry |
| Content Type | Text |
| Resource Type | Article |
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