Cyclooxygenases

Enzyme belonging to the enzyme family of oxygenases , which catalyses the formation of cyclic endoperoxides from unsaturated fatty acids.

A distinction is made between two forms, cyclooxygenase-1 (COX 1) and cyclooxygenase-2 (COX2). Both enzymes are very similar in their protein structure, but differ greatly in their function. While cyclooxygenase 1 is constitutively present in almost all cells and is responsible for the physiological concentrations of prostaglandins, cyclooxygenase 2 is induced in many cells in response to cell damage, inflammation or cell activation by agonists such as cytokines and growth factors.

Cyclooxygenases (COX1/COX2) are the rate-determining enzymes in the synthesis of prostaglandins from arachidonic acid. Cyclooxygenase-2 (COX2) is encoded on chromosome 1q25.2-q25.3. The COX-2 gene is a compact (8 kb), rapidly inducible gene that can be activated by, among other things, UV radiation. Thus, UV-mediated production of prostaglandins increases in the skin. However, transcription of the COX-2 gene is inducible in many ways.

Cyclooxygenases are localized inside the endoplasmic reticulum, within the nuclear envelope, and in the Golgi apparatus and adhere to the inner surfaces of the membranes of these cellular compartments. COX2 is found in the endothelial cells of proliferating blood vessels of inflammatory tissues and in the endothelial cells and phagocytes of atherosclerotic plaques (COX1 is found in endothelial cells of normal blood vessels).

In the spinal cord, COX2 is always present and is involved in pain stimulus processing there. COX-2 is increasingly transcribed during inflammatory processes, and the associated symptoms (fever, pain) can be effectively treated with COX-2 inhibitors (e.g., celecoxib) without the side effects of inhibiting cyclooxygenase-1 (e.g., on kidneys and stomach).

Oncology: COX2 is highly increased in numerous tumors, such as actinic keratoses and spinocellular carcinomas of the skin. Since COX2 stimulates the formation of vascular endothelial growth factor ( VEGF) via prostaglandin E2 and thus promotes angiogenesis, it is suspected that COX2 may play a role in tumor growth. Prostaglandins produced in tumor tissue, particularly PGE2, may affect both the tumor stroma (angiogenesis, immunosuppression) and tumor cells directly (proliferation, inhibition of apoptosis) in a variety of ways. It is possible that cyclooxygenases also influence the development of Alzheimer's disease.

1. Berking C (2007) Photocarcinogenesis. dermatologist 58: 398-405