15-Deoxy-Δ12,14-prostaglandin J2

15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is a metabolite of the cyclooxygenase pathway of arachidonic acid metabolism. It is a member of the J series of prostaglandins that have been identified as being formed when prostaglandin D2 (PGD2) undergoes dehydration.

Biosynthesis

The biosynthesis of 15d-PGJ2 is initiated by the enzyme cyclooxygenase-2 (COX-2), which converts arachidonic acid to prostaglandin H2 (PGH2). PGH2 is then converted to prostaglandin D2 (PGD2) by the enzyme prostaglandin D synthase. PGD2 is then dehydrated to form PGJ2, which is further dehydrated to form 15d-PGJ2.

Biological effects

15d-PGJ2 has been shown to have several biological effects. It is a potent agonist of the peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor that regulates gene expression involved in adipogenesis, lipid metabolism, and inflammation. Activation of PPARγ by 15d-PGJ2 has been shown to inhibit the proliferation of cancer cells and to induce apoptosis.

In addition to its effects on PPARγ, 15d-PGJ2 has been shown to inhibit the nuclear factor kappa B (NF-κB) pathway, which is involved in the regulation of immune responses, inflammation, and cell survival. Inhibition of NF-κB by 15d-PGJ2 has been shown to have anti-inflammatory effects.

Clinical significance

Due to its anti-inflammatory and anti-proliferative effects, 15d-PGJ2 has been investigated for its potential therapeutic applications in a variety of diseases, including cancer, rheumatoid arthritis, and neurodegenerative diseases.