Meta-Biol

• Pathways

In the absence of aspirin, dimeric cyclooxygenase 2 (PTGS2 aka COX2) located on the ER membrane can mediate the oxidation of docosahexaenoic acid (DHA) to 13-hydroxy-docosahexaenoic acid (13-HDHA) in activated macrophages (Serhan et al. 2002, Groeger et al. 2010). PTGS2 is an inducible enzyme expressed at sites of inflammation, infection and cancer where it can generate prostanoids that drive disease pathogenesis. It is the therapeutic target for nonsteroidal antiinflammatory drugs (NSAIDs) such as aspirin. PTGS2 is also constitutively expressed in specific tissues, especially the kidney, gastrointestinal tract, brain and thymus. Constitutive PTGS2 expression is increasingly being recognised to play a major role in homeostatic function in those tissues and is therapeutically important because NSAIDs cause cardiovascular and renal side effects in otherwise healthy individuals (Kirkby et al. 2016).