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Signalling networks regulating cyclooxygenase-2
Christos Tsatsanis1, Ariadne Androulidaki, Maria Venihaki
1Department of Clinical Chemistry-Biochemistry, School of Medicine, University of Crete, Heraklion, Crete GR-710 03, Greece. tsatsani@med.uoc.gr
Summary
Cyclooxygenase-2 (COX-2), a key inflammation enzyme, is regulated by extracellular signals via mitogen-activated protein kinases (MAPK). Targeting COX-2
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Cyclooxygenase-2 (COX-2) is a crucial enzyme in prostaglandin synthesis, mediating inflammation.
- COX-2 expression is upregulated by pro-inflammatory and growth signals.
- Mitogen-activated protein kinases (MAPK) pathway activation is central to COX-2 induction.
Purpose of the Study:
- To elucidate the regulatory mechanisms of Cyclooxygenase-2 (COX-2) expression and activity.
- To identify potential therapeutic targets within the COX-2 regulatory pathways.
Main Methods:
- Analysis of signaling pathways converging on COX-2.
- Investigation of transcriptional and post-transcriptional regulation of COX-2 mRNA.
- Examination of direct enzymatic modulation of COX-2 activity.
Main Results:
- Extracellular signals activate MAPK, influencing COX-2 mRNA at transcriptional and post-transcriptional levels.
- Transcription factors like CREB, NFkB, and C/EBP regulate COX-2 mRNA expression.
- mRNA stability and direct inhibition by nitric oxide (NO) and inducible nitric oxide synthase (iNOS) also affect COX-2.
Conclusions:
- COX-2 regulation is a complex, multi-step process involving signaling pathways, transcription factors, and mRNA stability.
- Each regulatory step presents a potential target for therapeutic intervention in inflammatory conditions.
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