Details zur Publikation |
| Kategorie | Textpublikation |
| Referenztyp | Zeitschriften |
| DOI | 10.1161/01.ATV.20.5.1209 |
| Titel (primär) | Heme oxygenase-1 is a cGMP-inducible endothelial protein and mediates the cytoprotective action of nitric oxide |
| Autor | Polte, T.; Abate, A.; Dennery, P.A.; Schröder, H. |
| Quelle | Arteriosclerosis Thrombosis and Vascular Biology |
| Erscheinungsjahr | 2000 |
| Department | IMMU |
| Band/Volume | 20 |
| Heft | 5 |
| Seite von | 1209 |
| Seite bis | 1215 |
| Sprache | englisch |
| Keywords | cGMP; cytoprotection; endothelial cells; heme oxygenase-1; nitric oxide |
| Abstract | Inducible heme oxygenase (HO-1) has recently been recognized as an antioxidant and cytoprotective gene. By use of Western blotting, cell viability analysis, and antisense technique, the present study investigates the involvement of HO-1 in endothelial protection induced by the clinically used nitric oxide (NO) donor molsidomine (specifically, its active metabolite 3-morpholinosydnonimine [SIN-1]) and the second messenger cGMP. In bovine pulmonary artery endothelial cells, SIN-1 and S-nitroso-N-acetyl-D,L-penicillamine (SNAP) at 1 to 100 mu mol/L induced the synthesis of HO-1 protein in a concentration-dependent fashion up to 3-fold over basal levels. HO-1 induction by SIN-1 was inhibited in the presence of the NO scavenger phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide and the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one. 8-Bromo-cGMP (1 to 100 mu mol/L) and dibutyryl cGMP (1 to 100 mu mol/L) as well as the activator of particulate guanylyl cyclase atrial natriuretic peptide (1 to 100 nmol/L) produced increases in HO-1 protein similar to those produced by SIN-1. SIN-1 and 8-bromo-cGMP increased heme oxygenase activity (bilirubin formation). Cytoprotection by NO donors was abrogated in the presence of the heme oxygenase inhibitor tin protoporphyrin IX, Pretreatment of cells with a phosphorothioate-linked HO-1 antisense oligonucleotide prevented protection by SIN-1 or 8-bromo-cGMP against tumor necrosis factor-ct cytotoxicity, whereas sense and scrambled HO-1 were without effect under these conditions. Our results show for the first time that HO-1 is a cGMP-sensitive endothelial gene and establish conclusively a causal relationship between HO-1 induction and endothelial protection by the NO/cGMP system. By targeting cytoprotective HO-1, NO donors may therefore be expected to induce antioxidant, antiatherogenic, and anti-inflammatory effects |
| dauerhafte UFZ-Verlinkung | https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=7517 |
| Polte, T., Abate, A., Dennery, P.A., Schröder, H. (2000): Heme oxygenase-1 is a cGMP-inducible endothelial protein and mediates the cytoprotective action of nitric oxide Arterioscler. Thromb. Vasc. Biol. 20 (5), 1209 - 1215 10.1161/01.ATV.20.5.1209 |
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