Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Brkić, L; Riederer, M; Graier, WF; Malli, R; Frank, S.
Acyl chain-dependent effect of lysophosphatidylcholine on cyclooxygenase (COX)-2 expression in endothelial cells.
Atherosclerosis. 2012; 224(2):348-354
Doi: 10.1016/j.atherosclerosis.2012.07.038
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- Leading authors Med Uni Graz
- Brkic Lada
- Frank Sasa
- Co-authors Med Uni Graz
- Graier Wolfgang
- Malli Roland
- Riederer Monika
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- Abstract:
- Objective: Previously we identified palmitoyl-, oleoyl-linoleoyl-, and arachidonoyl-lysophosph-atidylcholine (LPC 16:0, 18:1, 18:2 and 20:4) as the most prominent LPC species generated by endothelial lipase (EL). In the present study, we examined the capacity of those LPC to modulate expression of cyclooxygenase (COX)-2 in vascular endothelial cells. Methods & results: LPC 16:0 and 20:4 promoted both COX-2 mRNA-and protein synthesis with different potencies and kinetics. While LPC 18:1 induced a weak and transient increase in COX-2 mRNA, but not protein, LPC 18:2 increased COX-2 protein, without impacting mRNA. Chelation of intracellular Ca2+ and inhibition of p38 MAPK markedly attenuated 16:0 LPC- and 20:4 LPC- elicited induction of COX-2 expression, whereas inhibition of phospholipase C (PLC) attenuated only the effect of 16:0 LPC. LPC 16:0 and 20:4 differed markedly in their potencies to increase cytosolic Ca2+ concentration and in the kinetics of p38 MAPK activation. While the effects of 16:0 and 20:4 LPC on COX-2 expression were profoundly sensitive to silencing of either c-Jun or p65 (NF-kappa B), respectively, silencing of cyclic AMP responsive element binding protein (CREB) attenuated markedly the effect of both LPC. Conclusion: Our results indicate that the tested LPC species are capable of inducing COX-2 expression, whereby the efficacy and the relative contribution of underlying signaling mechanisms markedly differ, due to the length and degree of saturation of LPC acyl chains. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Calcium - metabolism
- Cell Line -
- Chelating Agents - pharmacology
- Cyclic AMP Response Element-Binding Protein - genetics
- Cyclooxygenase 2 - genetics
- Endothelial Cells - drug effects
- Gene Expression Regulation, Enzymologic - drug effects
- Humans -
- JNK Mitogen-Activated Protein Kinases - genetics
- Kinetics -
- Lysophosphatidylcholines - chemistry
- Molecular Structure -
- Protein Kinase Inhibitors - pharmacology
- RNA Interference -
- RNA, Messenger - metabolism
- Structure-Activity Relationship -
- Transcription Factor RelA - genetics
- Transfection -
- Up-Regulation -
- p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors
- Find related publications in this database (Keywords)
- Lysophosphatidylcholine
- COX-2
- Endothelial cells
- Calcium
- Acyl-chain
- Cell signaling