Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Leis, HJ; Zach, D; Huber, E; Windischhofer, W.
Prostaglandin endoperoxide synthase-2 contributes to the endothelin/sarafotoxin-induced prostaglandin E2 synthesis in mouse osteoblastic cells (MC3T3-E1): evidence for a protein tyrosine kinase-signaling pathway and involvement of protein kinase C.
Endocrinology. 1998; 139(3):1268-1277
Doi: 10.1210%2Fen.139.3.1268
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- Führende Autor*innen der Med Uni Graz
- Leis Hans-Joerg
- Co-Autor*innen der Med Uni Graz
- Windischhofer Werner
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- Abstract:
- Endothelin (ET) peptides are potent growth factors binding to G protein-coupled receptors. Sarafotoxins (S6) isolated from Atractaspis engaddensis are highly homologous to endothelins. In this study, we have investigated the effects of endothelin/sarafotoxin peptides on the prostaglandin synthesizing system in an osteoblast-like cell line, MC3T3-E1. ET-1, ET-2, beta-ET, and S6b rapidly stimulated prostaglandin E2 production within 5 min, whereas ET-3, S6a, and S6c did not. ET-1, ET-2, beta-ET, S6b, and S6a induced prostaglandin synthesis after 3 h of incubation. Antagonizing these effects with BQ-123, PD 142893, BQ-788, and S6c suggests signaling through an ET(A) receptor subtype in osteoblasts. Long-term prostaglandin synthesis was blocked by NS-398, and reduced to short-term levels by cycloheximide and actinomycin D, indicating induction of PGHS-2. There was only minor enhancement of cAMP accumulation by the agonists, which had no effect on prostaglandin synthesis. Induction of PGHS-2 was furthermore demonstrated by Northern blot analysis of PGHS-2 messenger RNA. Depletion of protein kinase C with TPA largely blunted the response. Genistein, an inhibitor of protein tyrosine kinases, also blocked long-term prostaglandin E2 formation. We conclude that in osteoblast-like MC3T3-E1 cells, ET-1, ET-2, beta-ET, S6b, and S6a peptides induce PGHS-2 through a protein tyrosine kinase-dependent and protein kinase C-dependent pathway, signaling through ET(A) receptor occupancy.
- Find related publications in this database (using NLM MeSH Indexing)
- 3T3 Cells -
- Animals -
- Cyclic AMP - biosynthesis
- Dinoprostone - biosynthesis
- Endothelins - pharmacology
- Mice - pharmacology
- Nitrobenzenes - pharmacology
- Osteoblasts - metabolism
- Prostaglandin-Endoperoxide Synthases - genetics
- Protein Kinase C - physiology
- Protein-Tyrosine Kinases - physiology
- RNA, Messenger - analysis
- Receptors, Endothelin - physiology
- Sulfonamides - pharmacology
- Viper Venoms - pharmacology