prostaglandin-d2 and Liver-Diseases

Lipocalin-type prostaglandin D synthase was previously known as β-trace protein (BTP), a low-molecular-weight glycoprotein that is heavily expressed in human cerebrospinal fluid. Nevertheless, it is also seen to be expressed in numerous other tissues including the kidney, liver, lung, heart, adipose, muscle, and pancreas. Functionally, L-PGDS behaves like a lipocalin type protein where it helps in binding and transportation of small lipophilic substances, such as steroids, retinoids, and other lipophilic ligands. Enzymatically, L-PGDS functions as a prostaglandin synthase where it helps in the production of PGD

Topics: Humans; Intramolecular Oxidoreductases; Lipocalins; Liver Diseases; Prostaglandin D2

Topics: Animals; Antioxidants; Apoptosis; Autophagy; Kupffer Cells; Liver; Liver Diseases; Male; Mice, Inbred BALB C; Prostaglandin D2; Protective Agents; Reactive Oxygen Species; Reperfusion Injury

The function of peroxisome proliferator-activated receptor-gamma (PPARgamma) in hepatic inflammation and injury is unclear. In this study, we sought to determine the role of PPARgamma in hepatic ischemia/reperfusion injury in mice. Male mice were subjected to 90 minutes of partial hepatic ischemia followed by up to 8 hours of reperfusion. PPARgamma was found to be constitutively activated in hepatocytes but not in nonparenchymal cells. Upon induction of ischemia, hepatic PPARgamma activation rapidly decreased and remained suppressed throughout the 8-hour reperfusion period. This reduced activation was not a result of decreased protein availability as hepatic nuclear PPARgamma, retinoid X receptor-alpha (RXRalpha), and PPARgamma/RXRalpha heterodimer expression was maintained. Accompanying the decrease in PPARgamma activation was a decrease in the expression of the natural ligand 15-deoxy-Delta(12,14)-prostaglandin J(2). This was associated with reduced interaction of PPARgamma and the coactivator, p300. To determine whether PPARgamma activation is hepatoprotective during hepatic ischemia/reperfusion injury, mice were treated with the PPARgamma agonists, rosiglitazone and connecting peptide. These treatments increased PPARgamma activation and reduced liver injury compared to untreated mice. Furthermore, PPARgamma-deficient mice had more liver injury after ischemia/reperfusion than their wild-type counterparts.. These data suggest that PPARgamma is an important endogenous regulator of, and potential therapeutic target for, ischemic liver injury.

Topics: Animals; C-Peptide; E1A-Associated p300 Protein; Gene Expression Regulation; Hepatocytes; Liver; Liver Diseases; Male; Mice; Mice, Inbred C57BL; PPAR gamma; Prostaglandin D2; Reperfusion Injury; Retinoid X Receptor alpha; Rosiglitazone; Thiazolidinediones

We demonstrate here for the first time that the endogenous cyclopentenone prostaglandin 15-deoxy-Delta12,14-prostaglandin J2 (15d-prostaglandin J2) reduces the liver injury (rise in serum transaminases) caused by severe endotoxaemia (6 mg/kg Escherichia coli endotoxin i.v. for 6 h) in the anaesthetised rat. The protection of the liver afforded by this potent agonist of PPAR-gamma was not secondary to a haemodynamic effect. Thus, 15d-prostaglandin J2 and other PPAR-gamma agonists may be useful in the therapy of septic shock.

Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents; Aspartate Aminotransferases; Endotoxins; Escherichia coli; Ligands; Liver Diseases; Male; Prostaglandin D2; Rats; Rats, Wistar; Receptors, Cytoplasmic and Nuclear; Shock, Septic; Transcription Factors