The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
David Bishopbailey - One of the best experts on this subject based on the ideXlab platform.
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endothelial cell apoptosis induced by the peroxisome proliferator activated receptor ppar ligand 15 deoxy delta12 14 Prostaglandin J2
Journal of Biological Chemistry, 1999Co-Authors: David BishopbaileyAbstract:Abstract 15-Deoxy-Δ12,14-Prostaglandin J2 (15d-PGJ2) is a bioactive prostanoid produced by dehydration and isomerization of PGD2, a cyclooxygenase product. It was recently shown to activate the nuclear peroxisome proliferator-activated receptor γ (PPARγ), a critical transcription factor involved in adipocyte and monocyte differentiation. In this report, we show that 15d-PGJ2 is a potent inducer of caspase-mediated endothelial cell apoptosis. PPARα, -δ, and -γ were expressed by endothelial cells, which, when treated with 15d-PGJ2, induced receptor translocation into the nucleus, and an increase in PPAR response element-driven reporter gene expression. Ciglitizone, a selective activator of PPARγ, also induced transcriptional activation and endothelial cell apoptosis. Endothelial apoptosis induced by 15d-PGJ2 was inhibited by treatment of cells with an oligonucleotide decoy to a consensus PPAR response element sequence. Furthermore, overexpression of the PPARγ isotype induced endothelial cell apoptosis, which was further potentiated by 15d-PGJ2 treatment. We conclude that 15d-PGJ2induces endothelial cell apoptosis via a PPAR-dependent pathway. The PPAR pathway may be a therapeutic target for numerous pathologies in which excessive angiogenesis is implicated.
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endothelial cell apoptosis induced by the peroxisome proliferator activated receptor ppar ligand 15 deoxy delta12 14 Prostaglandin J2
Journal of Biological Chemistry, 1999Co-Authors: David Bishopbailey, Timothy HlaAbstract:15-Deoxy-Delta12,14-Prostaglandin J2 (15d-PGJ2) is a bioactive prostanoid produced by dehydration and isomerization of PGD2, a cyclooxygenase product. It was recently shown to activate the nuclear peroxisome proliferator-activated receptor gamma (PPARgamma), a critical transcription factor involved in adipocyte and monocyte differentiation. In this report, we show that 15d-PGJ2 is a potent inducer of caspase-mediated endothelial cell apoptosis. PPARalpha, -delta, and -gamma were expressed by endothelial cells, which, when treated with 15d-PGJ2, induced receptor translocation into the nucleus, and an increase in PPAR response element-driven reporter gene expression. Ciglitizone, a selective activator of PPARgamma, also induced transcriptional activation and endothelial cell apoptosis. Endothelial apoptosis induced by 15d-PGJ2 was inhibited by treatment of cells with an oligonucleotide decoy to a consensus PPAR response element sequence. Furthermore, overexpression of the PPARgamma isotype induced endothelial cell apoptosis, which was further potentiated by 15d-PGJ2 treatment. We conclude that 15d-PGJ2 induces endothelial cell apoptosis via a PPAR-dependent pathway. The PPAR pathway may be a therapeutic target for numerous pathologies in which excessive angiogenesis is implicated.
Timothy Hla - One of the best experts on this subject based on the ideXlab platform.
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feedback control of the arachidonate cascade in rheumatoid synoviocytes by 15 deoxy delta 12 14 Prostaglandin J2
Biochemical and Biophysical Research Communications, 2001Co-Authors: Yasunori Tsubouchi, Timothy Hla, Yutaka Kawahito, Masataka Kohno, Kenichiro Inoue, Hajime SanoAbstract:Rheumatoid arthritis (RA) is a chronic polyarticular joint disease associated with massive synovial proliferation, inflammation, and angiogenesis. PPAR-gamma ligands, both 15-deoxy-Delta(12,14)-Prostaglandin J2 (15d- PGJ2) and troglitazone (TRO), can inhibit the growth of RA synoviocytes in vitro, and suppress the chronic inflammation of adjuvant-induced arthritis in rats, but the potency of 15d-PGJ2 is higher than TRO. Prostaglandin (PG) E2 plays important roles in joint erosion and synovial inflammation. In the present study, 15d-PGJ2, but not TRO and other prostanoids, suppressed interleukin (IL)-1beta-induced PGE2 synthesis in rheumatoid synovial fibroblasts (RSFs) through the inhibition of cyclooxygenase (COX-2) and cytosolic phospholipase A2 (cPLA2) expression. Furthermore, the inhibition was not affected by pretreatment with anti-PPAR-gamma antibody. It means that this anti-inflammatory effect of 15d-PGJ2 for PG synthesis may be independent of PPAR-gamma and 15d-PGJ2 is a key regulator of negative feedback of the arachidonate cascade on the COX pathway. These findings provide new insight into the feedback mechanism of the arachidonate cascade.
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endothelial cell apoptosis induced by the peroxisome proliferator activated receptor ppar ligand 15 deoxy delta12 14 Prostaglandin J2
Journal of Biological Chemistry, 1999Co-Authors: David Bishopbailey, Timothy HlaAbstract:15-Deoxy-Delta12,14-Prostaglandin J2 (15d-PGJ2) is a bioactive prostanoid produced by dehydration and isomerization of PGD2, a cyclooxygenase product. It was recently shown to activate the nuclear peroxisome proliferator-activated receptor gamma (PPARgamma), a critical transcription factor involved in adipocyte and monocyte differentiation. In this report, we show that 15d-PGJ2 is a potent inducer of caspase-mediated endothelial cell apoptosis. PPARalpha, -delta, and -gamma were expressed by endothelial cells, which, when treated with 15d-PGJ2, induced receptor translocation into the nucleus, and an increase in PPAR response element-driven reporter gene expression. Ciglitizone, a selective activator of PPARgamma, also induced transcriptional activation and endothelial cell apoptosis. Endothelial apoptosis induced by 15d-PGJ2 was inhibited by treatment of cells with an oligonucleotide decoy to a consensus PPAR response element sequence. Furthermore, overexpression of the PPARgamma isotype induced endothelial cell apoptosis, which was further potentiated by 15d-PGJ2 treatment. We conclude that 15d-PGJ2 induces endothelial cell apoptosis via a PPAR-dependent pathway. The PPAR pathway may be a therapeutic target for numerous pathologies in which excessive angiogenesis is implicated.
Jaroslaw Aronowski - One of the best experts on this subject based on the ideXlab platform.
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neuronal expression of peroxisome proliferator activated receptor gamma pparγ and 15d Prostaglandin J2 mediated protection of brain after experimental cerebral ischemia in rat
Brain Research, 2006Co-Authors: Xiurong Zhao, Lise A Labiche, Roger Strong, James C Grotta, Oliver Herrmann, Jaroslaw AronowskiAbstract:Abstract Existing experimental evidence suggests that PPARγ may play a beneficial role in neuroprotection from various brain pathologies. Here we found that focal cerebral ischemia induced by middle cerebral/common carotid arteries occlusion (MCA/CCAo) induced up-regulation of PPARγ messenger RNA in the ischemic hemisphere as early as 6 h after the ischemic event. The increased PPARγ mRNA expression was primarily associated with neurons in the ischemic penumbra, suggesting an important role for PPARγ in neurons after ischemia. Intraventricular injection of 15d-Δ12,14-Prostaglandin J2 (15d-PGJ2), a proposed endogenous PPARγ agonist, into the ischemic rat brains significantly increased the PPARγ-DNA-binding activity and reduced infarction volume at 24 h after reperfusion. We propose that PPARγ up-regulation in response to ischemia may contribute to PPARγ activation in the presence of PPARγ agonists. Activation of PPARγ in neurons at an early stage after ischemia may represent a pro-survival mechanism against ischemic injury.
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15d Prostaglandin J2 activates peroxisome proliferator activated receptor γ promotes expression of catalase and reduces inflammation behavioral dysfunction and neuronal loss after intracerebral hemorrhage in rats
Journal of Cerebral Blood Flow and Metabolism, 2006Co-Authors: Xiurong Zhao, Roger Strong, James C Grotta, Yujian Zhang, Jaroslaw AronowskiAbstract:Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a transcription factor that regulates the expression of various gene products that are essential in lipid and glucose metabolism, as well as that of the peroxisome-enriched antioxidant enzyme, catalase. Activation of PPARgamma is linked to anti-inflammatory activities and is beneficial for cardiovascular diseases. However, little is known about its role in intracerebral hemorrhage (ICH). 15-Deoxy-Delta(12,14)-Prostaglandin J2 (15d-PGJ2) acts as a physiologic agonist for PPARgamma. In this study, we found that injection of 15d-PGJ2 into the locus of striatal hematoma increased PPARgamma-deoxyribonucleic acid (DNA) binding activity and the expression of catalase messenger ribonucleic acid (mRNA) and protein in the perihemorrhagic area. Additionally, 15d-PGJ2 significantly reduced nuclear factor-kappaB (NF-kappaB) activation and prevented neutrophil infiltration measured by myeloperoxidase (MPO) immunoassay, and also reduced cell apoptosis measured by terminal deoxynucleotide transferase dUTP nick-end labeling (TUNEL). In addition, 15d-PGJ2 reduced behavioral dysfunction produced by the ICH. Altogether, our findings indicate that injection of 15d-PGJ2 at the onset of ICH is associated with activation of PPARgamma and elevation of catalase expression, suppression of NF-kappaB activity, and restricted neutrophil infiltration. All these events predicted reduced behavioral deficit and neuronal damage.
Luisa Minghetti - One of the best experts on this subject based on the ideXlab platform.
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role of the peroxisome proliferator activated receptor gamma ppar gamma and its natural ligand 15 deoxy delta12 14 Prostaglandin J2 in the regulation of microglial functions
European Journal of Neuroscience, 2000Co-Authors: Antonietta Bernardo, Giulio Levi, Luisa MinghettiAbstract:The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of a large group of nuclear receptors controlling the proliferation of peroxisomes that is involved in the downregulation of macrophage functions. Here, we report that PPAR-gamma was constitutively expressed in rat primary microglial cultures and that such expression was downregulated during microglial activation by endotoxin (LPS). The presence of the PPAR-gamma natural ligand 15-deoxy-Delta12,14-Prostaglandin J2 (15d-PGJ2) counteracted the repression of PPAR-gamma expression caused by LPS. In microglial cultures stimulated by LPS, interferon-gamma (IFN-gamma) or by their combination, 15d-PGJ2 reduced the production of nitric oxide (NO) and the expression of inducible NO synthase (iNOS). The inhibitory effect was dose-dependent and did not involve an elevation of cyclic AMP, a second messenger known to inhibit NOS expression in microglia. In addition, 15d-PGJ2 down-regulated other microglial functions, such as tumour necrosis factor-alpha (TNF-alpha) synthesis and major histocompatibility complex class II (MHC class II) expression. The effects of 15d-PGJ2 occurred, at least in part, through the repression of two important transcription factors, the signal transducer and activator of transcription 1 and the nuclear factor kappaB, known to mediate IFN-gamma and LPS cell signalling. Our observations suggest that 15d-PGJ2, the synthesis of which is likely to occur within the brain, could play an important role in preventing brain damage associated with excessive microglial activation.
Jidong Cheng - One of the best experts on this subject based on the ideXlab platform.
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peroxisome proliferator activated receptor γ ligands 15 deoxy δ12 14 Prostaglandin J2 and ciglitazone induce growth inhibition and cell cycle arrest in hepatic oval cells
Biochemical and Biophysical Research Communications, 2004Co-Authors: Jidong Cheng, Hideji Nakamura, Hiroyasu Imanishi, Takayuki Morisaki, Toshihiro Sugiyama, Toshikazu HadaAbstract:Abstract There is growing evidence to show that hepatic oval cells contribute to liver regeneration, dysplastic nodule formation, and hepato-carcinogenesis. Peroxisome proliferator-activated receptors (PPARs) and their ligands play an important role in cell growth, inflammatory responses, and liver pathogenesis including fibrosis and cancer. However, little is known about the role of PPARγ/its ligands in the growth and differentiation of hepatic oval cells. In this study, we found that OC15-5, a rat hepatic oval cell line, expressed PPARγ at mRNA and protein levels, and a natural ligand for PPARγ, 15-deoxy-Δ12,14-Prostaglandin J2 (15d-PGJ2), and a synthetic ligand, ciglitazone, inhibited growth of OC15-5 cells by arresting at G1-S in a dose-dependent manner. Apoptosis was also induced in OC15-5 cells by 15d-PGJ2 treatment. In OC15-5 cells treated with 15d-PGJ2, the expression of CDK inhibitor, p27Kip1, was up-regulated, while that of p21WAF1/Cip1, p18INK4C CDK2, CDK4, and cyclin E was unchanged. In addition, delayed up-regulation of AFP expression was observed in OC15-5 cells after 15d-PGJ2 or ciglitazone treatment. This is the first report to show that the PPARγ ligand was involved in the growth, cell cycle, and differentiation of hepatic oval cells, raising the possibility that the PPARγ ligands may regulate liver regeneration and hepato-carcinogenesis.
