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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kitz, K; Windischhofer, W; Leis, HJ; Huber, E; Kollroser, M; Malle, E.
15-Deoxy-Δ12,14-prostaglandin J2 induces Cox-2 expression in human osteosarcoma cells through MAPK and EGFR activation involving reactive oxygen species.
Free Radic Biol Med. 2011; 50(7):854-865
Doi: 10.1016/j.freeradbiomed.2010.12.039
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Kitz Kerstin
- Windischhofer Werner
- Co-Autor*innen der Med Uni Graz
- Huber Evelyn
- Kollroser Manfred
- Leis Hans-Joerg
- Malle Ernst
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- Abstract:
- Prostaglandins (PGs), important modulators in bone biology, may also contribute to tumor formation and progression in human osteosarcoma. 15-Deoxy-Δ(12,14)-PGJ(2) (15d-PGJ(2)), a metabolite of PGD(2) and PPARγ-ligand, exerts a panel of biological activities via receptor-dependent and -independent mechanisms. As inducible cyclooxygenase-2 (Cox-2) is a candidate inflammatory marker in human osteosarcoma and a rate-limiting enzyme in PG biosynthesis, this study aimed at investigating intracellular redox status and signaling cascades leading to Cox-2 induction in human MG-63 osteosarcoma cells. 15d-PGJ(2) induced the accumulation of reactive oxygen species (ROS) that in turn may lead to upregulation of Cox-2 via two different routes in a PPARγ-independent manner. First, phosphorylation of p38 MAPK directly enhances Cox-2 expression by promoting mRNA stability. Second, 15d-PGJ(2) induces activation of epidermal growth factor receptors and downstream activation of Cox-2 via phosphorylation of p42/44 MAPK. Glutathione precursor molecules reversed enhanced ROS levels and Cox-2 expression. Functional activity of Cox-2 expression was tested by measurement of PGE(2) and PGF(2α). The synthetic compound 9,10-dihydro-15d-PGJ(2) lacking the α,β-unsaturated carbonyl group in the cyclopentenone ring did not exhibit the cellular responses observed with 15d-PGJ(2). We conclude that the electrophilic carbon atom of 15d-PGJ(2) is responsible for alterations in intracellular redox status and Cox-2 expression.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cell Line, Tumor -
- Cyclooxygenase 2 - genetics
- Dinoprost - analysis
- Dinoprostone - analysis
- Gene Expression - drug effects
- Glutathione - metabolism
- Humans -
- Mice -
- Mitogen-Activated Protein Kinase 1 - genetics
- Mitogen-Activated Protein Kinase 3 - genetics
- Neoplasms -
- Osteosarcoma - genetics
- Oxidation-Reduction - drug effects
- Phosphorylation - drug effects
- Prostaglandin D2 - analogs & derivatives
- RNA Stability - genetics
- Reactive Oxygen Species - metabolism
- Receptor, Epidermal Growth Factor - genetics
- Signal Transduction - drug effects
- Up-Regulation -
- p38 Mitogen-Activated Protein Kinases - genetics
- Find related publications in this database (Keywords)
- ROS 15-Deoxy-Delta(12,14)-PGJ(2)
- Cyclooxygenase Epidermal growth factor receptor
- Mitogen-activated protein kinase
- Prostaglandins
- Eicosanoids Peroxisome proliferator-activated receptor
- NF-kappa B
- Free radicals