Disease relevance of Pparg

• CONCLUSIONS: PPAR gamma ligands may have beneficial effects on myocarditis by inhibiting MIP-1alpha expression and modulating the Th1/Th2 balance [1].
• Taken together, the results provide convincing evidence that PPAR-gamma agonists exert protective effects in a rat model of mild forebrain ischemia/reperfusion injury by inhibiting oxidative stress and excessive inflammatory response [2].
• Modulation of the oxidative stress and inflammatory response by PPAR-gamma agonists in the hippocampus of rats exposed to cerebral ischemia/reperfusion [2].
• The thiazolidinedione rosiglitazone (Avandia) is a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, that was recently approved by the Food and Drug Administration for treatment of type II diabetes mellitus [3].
• Our data suggest that decreased expression of PPAR-gamma protein in lungs may contribute to the ongoing pulmonary inflammation and tissue injury in endotoxemia [4].

Psychiatry related information on Pparg

• It has been reported that the expression of cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor-gamma (PPARgamma) is elevated in Alzheimer's disease, and certain nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risk and delay the onset of Alzheimer's disease [5].

High impact information on Pparg

• Several growth factors that inhibit fat cell differentiation caused mitogen-activated protein (MAP) kinase-mediated phosphorylation of the dominant adipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) and reduction of its transcriptional activity [6].
• A decrease in PPAR-gamma abolishes both the nuclear export of RelA and the anti-inflammatory activity of B. thetaiotaomicron [7].
• This PPAR-gamma-dependent anti-inflammatory mechanism defines new cellular targets for therapeutic drug design and interventions for the treatment of chronic inflammation [7].
• Troglitazone (CS-045) is one of the thiazolidinediones that activate the peroxisome proliferator-activated receptor gamma (PPARgamma), which is expressed primarily in adipose tissues [8].
• Thiazolidinediones repress ob gene expression in rodents via activation of peroxisome proliferator-activated receptor gamma [9].

Chemical compound and disease context of Pparg

• Pioglitazone, a peroxisome proliferator-activated receptor gamma activator, ameliorates experimental autoimmune myocarditis by modulating Th1/Th2 balance [1].
• The study investigates the effects of two PPAR-gamma agonists, rosiglitazone and pioglitazone, on oxidative stress and inflammatory response induced by ischemia/reperfusion in the rat hippocampus [2].
• The purpose of the present study was to investigate the profile of PPAR-gamma expression in the lung and to explore its functional significance in lipopolysaccharide (LPS)-induced acute lung injury [4].
• Peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists, including the glitazone class of drugs, are insulin sensitizers that reduce glucose and lipid levels in patients with type 2 diabetes mellitus [10].
• The anti-inflammatory effect of curcumin in an experimental model of sepsis is mediated by up-regulation of peroxisome proliferator-activated receptor-gamma [11].

Biological context of Pparg

• PPAR-gamma activation mediates adipose depot-specific effects on gene expression and lipoprotein lipase activity: mechanisms for modulation of postprandial lipemia and differential adipose accretion [12].
• These results indicate that PPAR-gamma can directly activate GK expression in liver and may contribute to improving glucose homeostasis in type 2 diabetes [13].
• Recent gene deletion studies indicate that PPARG and PPARD play critical roles in rodent development, including effects on placental vascularization [14].
• The PPAR-gamma receptor subtype appears to play a pivotal role in the regulation of cellular proliferation and inflammation [3].
• It has been reported that the mitogen-activated protein (MAP) kinase pathway inhibits PPAR-gamma function through its phosphorylation, and co-activator CREB-binding protein (CBP)/p300 interacts with PPAR-gamma and modulates its activity [15].

Anatomical context of Pparg

• Real-time reverse transcription-polymerase chain reaction and immunohistochemical analysis demonstrated markedly higher expression of Ppara, Pparg, and Rxra mRNA in labyrinth zone trophoblast as compared with basal zone near term [14].
• Activation of retinoic X receptor and peroxisome proliferator-activated receptor-gamma inhibits nitric oxide and tumor necrosis factor-alpha production in rat Kupffer cells [16].
• To explore the mechanism that fasting elevated BAT UCPs mRNA in VMH-lesioned rats, we measured peroxisome proliferator-activated receptor (PPAR)-gamma mRNA and protein in BAT, because PPAR-gamma agonist can elevate UCPs mRNA levels in BAT [17].
• Induction of cyclooxygenase-2 and peroxisome proliferator-activated receptor-gamma during nitric oxide-induced apoptotic PC12 cell death [5].
• We evaluated the effects of the PPAR-gamma activator rosiglitazone on Ang II signaling in aorta and mesenteric arteries [18].

Associations of Pparg with chemical compounds

• Maternal dexamethasone treatment (1 mug/ml in drinking water; Days 13-22, term = 23 days) reduced placental (44%) and fetal (31%) weights and resulted in a fall in Pparg (37%, P < 0.05) mRNA expression specifically in the labyrinth zone at Day 22 [14].
• An RXR-specific agonist, Ro47-5944, and a PPAR gamma-specific agonist, AD4833 (pioglitazone hydrochloride), each inhibited LPS-induced NO and TNF-alpha production [16].
• Agonists of EP2 (butaprost) and peroxisome proliferator-activated receptor gamma (ciglitazone) mimicked the effect of PGE(2) and 15d-PGJ(2), and an EP2 antagonist (AH6809) and a peroxisome proliferator-activated receptor gamma antagonist (GW9662) suppressed microglial death induced by LPS in combination with IL-13 [19].
• A role of PPAR-gamma in androstenediol-mediated salutary effects on cardiac function following trauma-hemorrhage [20].
• Recently, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), one of the natural ligands of peroxisome proliferator-activated receptor gamma (PPARgamma), has been reported to have an anti-inflammatory effect [21].

Physical interactions of Pparg

• Effects of mitogen-activated protein kinase pathway and co-activator CREP-binding protein on peroxisome proliferator-activated receptor-gamma-mediated transcription suppression of angiotensin II type 1 receptor gene [15].

Regulatory relationships of Pparg

• We have shown that the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands troglitazone and rosiglitazone inhibit VSMC migration downstream of ERK MAPK [22].
• Peroxisome proliferator-activated receptor gamma regulates angiotensin II-stimulated phosphatidylinositol 3-kinase and mitogen-activated protein kinase in blood vessels in vivo [18].
• Celecoxib and F-L-Leu, separately, inhibited COX-2 and up-regulated PPAR gamma expression [23].
• In cultured RAW 264.7 cells, curcumin inhibited endotoxin-induced increases in TNF-alpha expression and markedly up-regulated PPAR-gamma expression without affecting cell viability [11].
• PPAR-gamma overexpression selectively suppresses insulin secretory capacity in isolated pancreatic islets through induction of UCP-2 protein [24].

Other interactions of Pparg

• CONCLUSION: The androstenediol-mediated salutary effects on cardiac function following T-H appear to be mediated at least in part via PPAR-gamma activation, which down-regulates IL-6 and iNOS gene expression in the heart [20].
• There was also a marked increase in Pparg (65%, P < 0.05) and Ppara (91%, P < 0.05) mRNA specifically in the labyrinth zone over the final third of pregnancy [14].
• Peroxisome proliferator-activated receptor gamma mediates protection against cyclooxygenase-2-induced gut dysfunction in a rodent model of mesenteric ischemia/reperfusion [25].
• It has been reported that the insulin sensitizers, thiazolidinediones (TZDs), increase UCP2 mRNA levels and, more recently, that TZDs stimulate UCP2 reporter genes but that the sequences involved do not bind peroxisome proliferator-activated receptor gamma (PPARgamma) [26].
• VSMC adhesion was not affected by the ERK MAPK pathway inhibitor PD98059 or PPAR-gamma ligands [22].

Analytical, diagnostic and therapeutic context of Pparg

• Rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand, has recently been shown to confer cardioprotection against ischemia-reperfusion in animal models [27].
• Western blot analyses revealed that peroxisome proliferator-activated receptor (PPAR) alpha is equally abundant in the liver and the testis, whereas PPAR gamma and retinoic acid receptor (RAR) alpha are expressed more in the testis [28].
• Diet-induced overweight rats showed higher PPAR gamma 1 (p<0.05) and lower SREBP-1 (p<0.01) mRNA expression levels with an inhibition of the DNA-binding ability of NF-kappa B compared to control rats as determined by gel-shift analysis [29].
• Peroxisome Proliferator-Activated Receptor-gamma Agonists Diminish Peritoneal Functional and Morphological Changes Induced by Bioincompatible Peritoneal Dialysis Solution [30].
• RESULTS: Reverse transcription-polymerase chain reaction (RT-PCR) showed the presence of PPAR-gamma and -alpha mRNA in rat mesangial cells [31].

References