Prorenin and Renin-Induced Extracellular Signal-Regulated Kinase 1/2 Activation in Monocytes Is Not Blocked by Aliskiren or the Handle-Region Peptide
| Autor: | Friedrich C. Luft, Anette Fiebeler, A.H. Jan Danser, Sandra Feldt, Maren Wellner, Geneviève Nguyen, Aurelie Contrepas, Wendy W. Batenburg, Michael Bader, Ulrike Maschke, Istvan Mazak, Heda Kvakan, Céline Burcklé, Ralf Dechend, Dominik N. Müller |
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| Přispěvatelé: | Internal Medicine |
| Rok vydání: | 2008 |
| Předmět: |
MAPK/ERK pathway
medicine.medical_specialty Biology Monocytes chemistry.chemical_compound Fumarates Internal medicine Renin Renin–angiotensin system Internal Medicine medicine Humans Phosphorylation Kinase activity Protein kinase A Cells Cultured Mitogen-Activated Protein Kinase 1 ATP6AP2 Mitogen-Activated Protein Kinase 3 Angiotensin II fungi U937 Cells Aliskiren Amides Molecular biology Enzyme Activation Endocrinology chemistry Signal transduction Peptides Oligopeptides Protein Binding Signal Transduction |
| Zdroj: | Hypertension, 51(3), 682-688. Lippincott Williams & Wilkins |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hypertensionaha.107.101444 |
| Popis: | The recently cloned (pro)renin receptor [(P)RR] mediates renin-stimulated cellular effects by activating mitogen-activated protein kinases and promotes nonproteolytic prorenin activation. In vivo, (P)RR is said to be blocked with a peptide consisting of 10 amino acids from the prorenin prosegment called the “handle-region” peptide (HRP). We tested whether human prorenin and renin induce extracellular signal-regulated kinase (ERK) 1/2 activation and whether the direct renin inhibitor aliskiren or the HRP inhibits the receptor. We detected the (P)RR mRNA and protein in isolated human monocytes and in U937 monocytes. In U937 cells, we found that both human renin and prorenin induced a long-lasting ERK 1/2 phosphorylation despite angiotensin II type 1 and 2 receptor blockade. In contrast to angiotensin II-ERK signaling, renin and prorenin signaling did not involve the epidermal growth factor receptor. A mitogen-activated protein kinase kinase 1/2 inhibitor inhibited both renin and prorenin-induced ERK 1/2 phosphorylation. Neither aliskiren nor HRP inhibited binding of 125 I-renin or 125 I-prorenin to (P)RR. Aliskiren did not inhibit renin and prorenin-induced ERK 1/2 phosphorylation and kinase activity. Fluorescence-activated cell sorter analysis showed that, although fluorescein isothiocyanate-labeled HRP bound to U937 cells, HRP did not inhibit renin or prorenin-induced ERK 1/2 activation. In conclusion, prorenin and renin-induced ERK 1/2 activation are independent of angiotensin II. The signal transduction is different from that evoked by angiotensin II. Aliskiren has no (P)RR blocking effect and did not inhibit ERK 1/2 phosphorylation or kinase activity. Finally, we found no evidence that HRP affects renin or prorenin binding and signaling. |
| Databáze: | OpenAIRE |
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