Journal ArticleDOI
Cyclopentenone prostaglandins: new insights on biological activities and cellular targets.
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TLDR
Recent progress is reviewed in understanding the mechanisms of action of the cyclopentenone prostaglandins and their possible use as therapeutic agents.Abstract:
The cyclopentenone prostaglandins PGA2, PGA1, and PGJ2 are formed by dehydration within the cyclopentane ring of PGE2, PGE1, and PGD2. PGJ2 is metabolized further to yield Delta(12)-PGJ(2) and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)). Various compounds within the cyclopentenone prostaglandin family possess potent anti-inflammatory, anti-neoplastic, and anti-viral activity. Most actions of the cyclopentenone prostaglandins do not appear to be mediated by binding to G-protein coupled prostanoid receptors. Rather, the bioactivity of these compounds results from their interaction with other cellular target proteins. 15-deoxy-Delta(12,14)-PGJ(2) is a high affinity ligand for the nuclear receptor PPARgamma and modulates gene transcription by binding to this receptor. Other activities of the cyclopentenone prostaglandins are mediated by the reactive alpha,beta-unsaturated carbonyl group located in the cyclopentenone ring. The transcription factor NF-kappaB and its activating kinase are key targets for the anti-inflammatory activity of 15d-PGJ2, which inhibits NF-kappaB-mediated transcriptional activation by PPARgamma-dependent and independent molecular mechanisms. Other cyclopentenone prostaglandins, such as Delta(7)-PGA1 and Delta(12)-PGJ2, have strong anti-tumor activity. These compounds induce cell cycle arrest or apoptosis of tumor cells depending on the cell type and treatment conditions. We review here recent progress in understanding the mechanisms of action of the cyclopentenone prostaglandins and their possible use as therapeutic agents.read more
Citations
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NPR1 Modulates Cross-Talk between Salicylate- and Jasmonate-Dependent Defense Pathways through a Novel Function in the Cytosol
Steven H. Spoel,Steven H. Spoel,Annemart Koornneef,Susanne M. C. Claessens,Jerome Korzelius,Johan A. Van Pelt,Martin J. Mueller,Antony Buchala,Jean-Pierre Métraux,Rebecca L. Brown,Kemal Kazan,L.C. van Loon,Xinnian Dong,Corné M. J. Pieterse +13 more
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References
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TL;DR: Recently, significant advances have been made in elucidating the details of the pathways through which signals are transmitted to the NF-kappa B:I kappa B complex in the cytosol and their implications for the study of NF-Kappa B.
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Michael Karin,Yinon Ben-Neriah +1 more
TL;DR: Recent progress has been made in understanding the details of the signaling pathways that regulate NF-kappaB activity, particularly those responding to the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1.
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The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation
Mercedes Ricote,Andrew C. Li,Andrew C. Li,Timothy M. Willson,Carolyn J. Kelly,Christopher K. Glass +5 more
TL;DR: It is shown that PPAR-γ is markedly upregulated in activated macrophages and inhibits the expression of the inducible nitric oxide synthase, gelatinase B and scavenger receptor A genes in response to 15d-PGJ2 and synthetic PPar-γ ligands, suggesting that PPARS and locally produced prostaglandin D2 metabolites are involved in the regulation of inflammatory responses.
Journal ArticleDOI
The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance.
John D. Hayes,David J. Pulford +1 more
TL;DR: The biochemical functions of GST are described to show how individual isoenzymes contribute to resistance to carcinogens, antitumor drugs, environmental pollutants, and products of oxidative stress, and to allow identification of factors that may modulate resistance to specific noxious chemicals.
Journal ArticleDOI
PPAR-γ agonists inhibit production of monocyte inflammatory cytokines
TL;DR: Inhibition of cytokine production may help to explain the incremental therapeutic benefit of NSAIDs observed in the treatment of rheumatoid arthritis at plasma drug concentrations substantially higher than are required to inhibit prostaglandin G/H synthase (cyclooxygenase).