The primary route of inactivation of the endocannabinoid 2-arachidonoylglycerol in the central nervous system is through enzymatic hydrolysis, mainly carried out by monoacylglycerol lipase (MAGL), along with a small contribution by the α/β-hydrolase domain (ABHD) proteins ABHD6 and ABHD12. Recent methodological progress allowing kinetic monitoring of glycerol liberation has facilitated substrat...

Microsomal prostaglandin E synthase (mPGES)-1 is a newly identified inducible enzyme of the arachidonic acid cascade with a key function in prostaglandin (PG)E2 synthesis. We investigated the kinetics of inducible cyclo-oxygenase (COX)-2 and mPGES-1 expression with respect to the production of 6-keto-PGF1alpha and PGE2 in rat chondrocytes stimulated with 10 ng/ml IL-1beta, and compared their mo...

Neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) appear to have no connection with cancers. In the view of cell death, however, common ground can be found between neuronal and non-neuronal diseases [1]. AD and PD are ascribed to the cell death of neurons, which should be alive under healthy conditions. In contrast, cancers are attributed to the proliferat...

introduction: the inflammatory response requires a coordinated integration of various signaling pathway including cyclooxygenase (cox). cox catalyzes the formation of prostaglandins from arachidonic acid. among prostaglandins, 15-deoxy-d12, 14-prostaglandin j2 (15d-pgj2), an endogenous ligand of peroxisome proliferator-activated receptor-gamma (ppar-γ), has been demonstrated to have anti-inflam...

We have previously shown that nuclear factorB inhibition by adenovirus expressing mutated I Bor by proteasome inhibitor increases human articular chondrocytes sensibility to apoptosis. Moreover, the nuclear factorB inhibitor BAY11-7085, a potent anti-inflammatory drug in rat adjuvant arthritis, is itself a proapoptotic agent for chondrocytes. In this work, we show that BAY 11-7085 but not the p...

15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is an electrophilic lipid mediator derived from PGD2 with potent anti-inflammatory effects. These are likely to be due to the covalent modification of cellular proteins, via a reactive α,β-unsaturated carbonyl group in its cyclopentenone ring. This study was carried out to identify novel cellular target(s) for covalent modification by 15d-PGJ2 and to ...

Liver fatty acid binding protein (L-FABP) is the principal target protein of the hepatic carcinogen N-(2-fluorenyl)acetamide (2-acetylaminofluorene) in rat liver. In addition, the cyclopentenone prostaglandins (PG), PGA, PGJ2, and delta 12-PGJ2, inhibit the growth of many cell types in vitro. This report describes the preferential binding of the growth inhibitory prostaglandins by L-FABP and th...

Prostaglandin D2 (PGD2), the predominant prostanoid produced by activated mast cells, is implicated in a variety of allergic diseases. PGD2 exerts its effects through two G-protein coupled receptors, DP and CRTH2. PGD2 mediates chemotaxis of eosinophils, basophils, and Th2 cells via CRTH2-evoked signaling, suggesting a role for this receptor in allergic disease. To characterize the mouse CRTH2 ...

Peroxisome proliferator-activated receptors (PPARs) have been originally thought to be restricted to lipid metabolism or glucose homeostasis. Recently, evidence is growing that PPARγ ligands have inhibitory effects on tumor growth. To shed light on the potential therapeutic effects on melanoma we tested a panel of PPAR agonists on their ability to block tumor proliferation in vitro. Whereas cig...

OBJECTIVE Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands reduce lesion formation in animal models of atherosclerosis by mechanisms that have not been defined completely. We hypothesized that PPARgamma ligands stimulate endothelial-derived nitric oxide release (*NO) to protect the vascular wall. METHODS AND RESULTS The PPARgamma ligands, 15-deoxy-Delta(12,14)-prostaglandi...