Cyclooxygenases

Enzymes belonging to the enzyme family of oxygenases that catalyze 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 coding COX-2 gene is a compact (8 kb), rapidly inducible gene that can be activated by UV radiation, among other things. This increases the UV-mediated production of prostaglandins in the skin. However, the transcription of the COX-2 gene can be induced in many different 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 cell compartments. COX2 is found in the endothelial cells of proliferating blood vessels of inflammatory tissue as well as in the endothelial cells and phagocytes of atherosclerotic plaques (COX1 is found in endothelial cells of normal blood vessels).

COX2 is always present in the spinal cord, where it is involved in the processing of pain stimuli. COX-2 is increasingly formed during inflammatory processes, 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 the kidneys and stomach).

Oncology: COX2 is strongly increased in numerous tumors, such as actinic keratoses and spinocellular carcinomas of the skin. Since COX2 stimulates the formation of vascular endothelial growth factors(VEGF) via prostaglandin E2 and thus promotes angiogenesis, it is assumed that COX2 could play a role in tumor growth.

The prostaglandins formed in tumor tissue, in particular PGE2, can influence both the tumor stroma (angiogenesis, immunosuppression) and tumor cells directly (proliferation, inhibition of apoptosis) in a variety of ways. Cyclooxygenases may also influence the development of Alzheimer's disease.

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