Disease relevance of prostaglandin J2

• Cyclopentenone prostaglandins (PGs) such as prostaglandin A1 (PGA1) and prostaglandin J2 (PGJ2) significantly increased the life span of Ehrlich ascites tumor-bearing mice [1].
• Prostaglandin J2 alters pro-survival and pro-death gene expression patterns and 26 S proteasome assembly in human neuroblastoma cells [2].
• Role of 15-deoxy delta(12,14) prostaglandin J2 and Nrf2 pathways in protection against acute lung injury [3].
• 15-Deoxy-Delta(12,14) prostaglandin J2 (15d-PGJ2) is a natural ligand for the peroxisome proliferator-activated receptor gamma (PPARgamma) that exhibits antiproliferative activity in colon cancer cells, but its mechanism of action is still poorly understood [4].
• Prostaglandin J2 metabolites inhibit aromatase activity by redox-sensitive mechanisms: potential implications for breast cancer therapy [5].

High impact information on prostaglandin J2

• A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation [6].
• PPAR-gamma is activated by a range of synthetic and naturally occurring substances, including antidiabetic thiazolidinediones, polyunsaturated fatty acids, 15-deoxy-delta prostaglandin J2 and components of oxidized low-density lipoprotein, such as 13-hydroxyoctadecadienoic acid (13-HODE) and 15-hydroxyeicosatetraenoic acid (15-HETE) [7].
• Our results indicated that the PPARgamma ligands 15-deoxy- prostaglandin J2 and GW1929 as well as PA induced LA-N-5 cells to differentiate to a similar phenotype as evidenced by inhibition of cell proliferation, neurite outgrowth, increased acetylcholinesterase activity, and decreased N-myc gene expression [8].
• We show that prostaglandin J2 (PGJ2), an endogenous product of inflammation, disrupts the cytoskeleton in neuronal cells [9].
• Cytoskeleton/endoplasmic reticulum collapse induced by prostaglandin J2 parallels centrosomal deposition of ubiquitinated protein aggregates [9].

Chemical compound and disease context of prostaglandin J2

• Murine J774.2 macrophages were stimulated with Escherichia coli lipopolysaccharide (concentration, 10 microg/mL) with or without the PPARgamma ligand, 15-deoxy-Delta prostaglandin J2 (15d-PGJ2), or the LXRalpha ligands, 22(R)-hydroxycholesterol and T0901317 (concentration range, 0.01-10 micromol/L), alone or in combination [10].
• 15-deoxy prostaglandin J2 enhances allyl alcohol-induced toxicity in rat hepatocytes [11].

Biological context of prostaglandin J2

• Inhibition of sequestosome 1/p62 up-regulation prevents aggregation of ubiquitinated proteins induced by prostaglandin J2 without reducing its neurotoxicity [12].
• This inhibition of adipogenesis is independent of the production of the peroxisome proliferator activated receptor gamma ligand prostaglandin J2, but dependent on the production of proliferative prostaglandins, such as prostaglandin E2 [13].
• 15d- prostaglandin J2 did not affect the biphasic fall in blood pressure or the increase in heart rate caused by administration of peptidoglycan+lipopolysaccharide [14].

Anatomical context of prostaglandin J2

• Inhibition of mesangial cell nitric oxide in MRL/lpr mice by prostaglandin J2 and proliferator activation receptor-gamma agonists [15].
• Although peroxisome proliferators, including fibrates and fatty acids, activate the transcriptional activity of these receptors, only prostaglandin J2 derivatives have been identified as natural ligands of the PPAR gamma subtype that also binds thiazolidinedione antidiabetic agents with high affinity [16].
• Upregulation of interleukin-8 expression by prostaglandin D2 metabolite 15-deoxy-delta12, 14 prostaglandin J2 (15d-PGJ2) in human THP-1 macrophages [17].
• However, recently it has been demonstrated that specific cyclopentone prostaglandin metabolites including 15-deoxy-Delta(12,14) prostaglandin J2 (15d-PGJ2) are capable of repressing the production of pro-inflammatory molecules by cells of the monocyte/macrophage lineage [18].
• Recently, we examined the role of PPARgamma in EAE and observed that administration of the PPARgamma agonist 15-deoxy-Delta(12,14) prostaglandin J2 exerted a significant therapeutic effect predominantly by inhibiting the activation and expansion of encephalitogenic T cells [19].

Associations of prostaglandin J2 with other chemical compounds

• PPAR alpha has been shown to bind and be activated by leukotriene B4 and fibrates, whereas prostaglandin J2 derivatives and the antidiabetic thiazolidinediones, respectively, are natural and synthetic ligands for PPAR gamma [20].
• In contrast, the PPARgammaligand prostaglandin J2 had no effect on protein or mRNA levels of involucrin or transglutaminase [21].
• 2-Cyclopenten-1-one and prostaglandin J2 reduce restenosis after balloon angioplasty in rats: role of NF-kappaB [22].
• In vivo treatment of SJL/J mice with PPARgamma agonists, 15-deoxydelta(12,14) prostaglandin J2 or Ciglitazone, decreased the duration and clinical severity of active immunization and adoptive transfer models of EAE [23].
• Prostaglandins containing an alpha,beta-unsaturated keto group, such as prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2), inhibit cell proliferation [24].

Gene context of prostaglandin J2

• Neurotoxic prostaglandin J2 enhances cyclooxygenase-2 expression in neuronal cells through the p38MAPK pathway: a death wish [25]?
• The recombinant protein of OPR3 cross-reacted with an antiserum raised against the OYE protein, and showed oxidation of beta-NADPH when OPDA or 15-deoxy-delta(12,14) prostaglandin J2 (PGJ2), an analogue of OPDA, was used as substrate [26].
• Opposite effects of prostaglandin-J2 on VEGF in normoxia and hypoxia: role of HIF-1 [27].
• Although peroxisome proliferators, including fibrates and fatty acids, activate the transcriptional activity of these receptors, only prostaglandin J2 derivatives have been identified as natural ligands of the PPAR gamma subtype, which also binds thiazolidinedione antidiabetic agents with high affinity [28].
• Differential regulation of chemokine gene expression by 15-deoxy-delta 12,14 prostaglandin J2 [29].

Analytical, diagnostic and therapeutic context of prostaglandin J2

• High performance liquid chromatography and TLC analyses showed that the metabolite behaved chromatographically similar to prostaglandin J2 and Delta12-prostaglandin J2 [30].

References