Cyclopentenone prostaglandins: Difference between revisions
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==Biochemistry== |
==Biochemistry== |
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In cells, [[COX-1]] |
In cells, [[COX-1]] and [[COX-2]] metabolize [[arachidonic acid]] to [[PGH2]] which is then converted to [[PGE2]] by any one of three [[isozymes]], [[PTGES]], [[PTGES2]], and [[PTGES3]] or, alternatively, to PGD2 by either of two enzymes, a [[glutathione]]-independent synthase termed lipocalin-type [[Prostaglandin D2 synthase]] (PTGDS or L-PGDS) and a glutathione-dependent hematopoietic-type H-[[PGDS]] or PTGDS2; the COX's also metabolizes [[dihomo-gamma-linolenic acid]] to PGH1 which is metabolized by one of the three PTGES isomzymes to [[PGE1]] (see [[eicosanoid#Prostanoid pathways]]). PGE2, PGE1, and PGD2 undergo a [[dehydration reaction]] PGA2, PGA1, and PGJ2, respectively. PGD2 conversions form the most studied cyclopentenone PGs. These conversions are as follows:<ref name="pmid21843512">{{cite journal | vauthors = Surh YJ, Na HK, Park JM, Lee HN, Kim W, Yoon IS, Kim DD | title = 15-Deoxy-Δ¹²,¹⁴-prostaglandin J₂, an electrophilic lipid mediator of anti-inflammatory and pro-resolving signaling | journal = Biochemical Pharmacology | volume = 82 | issue = 10 | pages = 1335–51 | year = 2011 | pmid = 21843512 | doi = 10.1016/j.bcp.2011.07.100 | url = }}</ref><ref name="pmid11301410">{{cite journal | vauthors = Straus DS, Glass CK | title = Cyclopentenone prostaglandins: new insights on biological activities and cellular targets | journal = Medicinal Research Reviews | volume = 21 | issue = 3 | pages = 185–210 | year = 2001 | pmid = 11301410 | doi = | url = }}</ref><ref name="pmid25269616">{{cite journal | vauthors = Rossitto M, Ujjan S, Poulat F, Boizet-Bonhoure B | title = Multiple roles of the prostaglandin D2 signaling pathway in reproduction | journal = Reproduction (Cambridge, England) | volume = 149 | issue = 1 | pages = R49–58 | year = 2015 | pmid = 25269616 | doi = 10.1530/REP-14-0381 | url = }}</ref> |
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*PGD2 is a 20 carbon [[arachidonic acid]] metabolite with [[double bond]]s between carbons 5,6 and 13,14, a carbon-carbon bond between carbons 8 and 12 (which establishes its [[cyclopentanone]] structure), [[hydroxyl]] residues attached to carbons 9 and 15, and a [[ketol]] residue attached to carbon 11. |
*PGD2 is a 20 carbon [[arachidonic acid]] metabolite with [[double bond]]s between carbons 5,6 and 13,14, a carbon-carbon bond between carbons 8 and 12 (which establishes its [[cyclopentanone]] structure), [[hydroxyl]] residues attached to carbons 9 and 15, and a [[ketol]] residue attached to carbon 11. |
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*PGD2 undergoes a dehydration reaction (i.e. removal of H<sub>2</sub>O) across 9-hydroxyl-carbon 10 to form a new 9,10 double bond and thus becomes PGJ2 with a cyclopentenone ring replacing the cyclopentanone ring. Carbon 9 thereby becomes chemically reactive as an [[electrophilic]] center. |
*PGD2 undergoes a dehydration reaction (i.e. removal of H<sub>2</sub>O) across 9-hydroxyl-carbon 10 to form a new 9,10 double bond and thus becomes PGJ2 with a cyclopentenone ring replacing the cyclopentanone ring. Carbon 9 thereby becomes chemically reactive as an [[electrophilic]] center. |
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==Mechanisms of action== |
==Mechanisms of action== |
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===G protein coupled receptors=== |
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The PGJ2 series of cyclopentenone PGs bind to and activate the [[Prostaglandin DP2 receptor]], with 15-deoxy-Δ12,14-PGJ2 and PDJ2 exhibiting potencies comparable to PGD2 (i.e. Ki [[equilibrium constants]] ~20-45 nanomolar) and Δ12-PGJ2 having 10-fold lesser potency, at least on mouse DP2 receptor.<ref name="pmid12721327">{{cite journal | vauthors = Hata AN, Zent R, Breyer MD, Breyer RM | title = Expression and molecular pharmacology of the mouse CRTH2 receptor | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 306 | issue = 2 | pages = 463–70 | year = 2003 | pmid = 12721327 | doi = 10.1124/jpet.103.050955 | url = }}</ref><ref name="pmid2674874">{{cite journal | vauthors = Bégué P, Quinet B, Baron S, Challier P, Fontaine JL, Lasfargues G | title = [Clinical and pharmacokinetic study of imipenem/cilastatin in children and newborn infants] | journal = Pathologie-biologie | volume = 37 | issue = 5 | pages = 485–90 | year = 1989 | pmid = 2674874 | doi = | url = }}</ref> These PGJ2's also bind and activate [[Prostaglandin DP1 receptor]] but require |
The PGJ2 series of cyclopentenone PGs bind to and activate the [[G protein-coupled receptor]], [[Prostaglandin DP2 receptor]], with 15-deoxy-Δ12,14-PGJ2 and PDJ2 exhibiting potencies comparable to PGD2 (i.e. Ki [[equilibrium constants]] ~20-45 nanomolar) and Δ12-PGJ2 having 10-fold lesser potency, at least on mouse DP2 receptor.<ref name="pmid12721327">{{cite journal | vauthors = Hata AN, Zent R, Breyer MD, Breyer RM | title = Expression and molecular pharmacology of the mouse CRTH2 receptor | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 306 | issue = 2 | pages = 463–70 | year = 2003 | pmid = 12721327 | doi = 10.1124/jpet.103.050955 | url = }}</ref><ref name="pmid2674874">{{cite journal | vauthors = Bégué P, Quinet B, Baron S, Challier P, Fontaine JL, Lasfargues G | title = [Clinical and pharmacokinetic study of imipenem/cilastatin in children and newborn infants] | journal = Pathologie-biologie | volume = 37 | issue = 5 | pages = 485–90 | year = 1989 | pmid = 2674874 | doi = | url = }}</ref> These PGJ2's also bind and activate a second G protein-coupled receptor, [[Prostaglandin DP1 receptor]], but require high concentrations to do so; this activation is not considered physiological.<ref name="pmid2674874">{{cite journal | vauthors = Bégué P, Quinet B, Baron S, Challier P, Fontaine JL, Lasfargues G | title = [Clinical and pharmacokinetic study of imipenem/cilastatin in children and newborn infants] | journal = Pathologie-biologie | volume = 37 | issue = 5 | pages = 485–90 | year = 1989 | pmid = 2674874 | doi = | url = }}</ref> DP2 and DP1 are [[G protein-coupled receptor]]s, with the DP2 receptor coupled to [[Gi alpha subunit]]-dependent depression of cellular [[cAMP]] levels and causing the potentiation cell injury in neural tissue cultures and with the DP1 receptor coupled to [[Gs alpha subunit]]-dependent increases in celluar cAMP levels and the suppression of cell injury in neural tissue cultures.<ref name="pmid2674874">{{cite journal | vauthors = Bégué P, Quinet B, Baron S, Challier P, Fontaine JL, Lasfargues G | title = [Clinical and pharmacokinetic study of imipenem/cilastatin in children and newborn infants] | journal = Pathologie-biologie | volume = 37 | issue = 5 | pages = 485–90 | year = 1989 | pmid = 2674874 | doi = | url = }}</ref> |
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===Peroxisome proliferator-activated receptor gamma=== |
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PGD2, PGJ2, Δ12-PGJ2, and 15-deoxy-Δ12,14-PGJ2 activate the [[transcription factor]], [[PPARγ]] with 15-deoxy-Δ12,14-PGJ2 being the most potent of the four PGs.<ref name="pmid8521497">{{cite journal | vauthors = Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, Evans RM | title = 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma | journal = Cell | volume = 83 | issue = 5 | pages = 803–12 | year = 1995 | pmid = 8521497 | doi = | url = }}</ref> Accordingly, studies |
PGD2, PGJ2, Δ12-PGJ2, and 15-deoxy-Δ12,14-PGJ2 activate the [[transcription factor]], [[PPARγ]], with 15-deoxy-Δ12,14-PGJ2 being the most potent of the four PGs.<ref name="pmid8521497">{{cite journal | vauthors = Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, Evans RM | title = 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma | journal = Cell | volume = 83 | issue = 5 | pages = 803–12 | year = 1995 | pmid = 8521497 | doi = | url = }}</ref> Accordingly, further studies have focused on 15-deoxy-Δ12,14-PGJ2. This PG directly binds with and activates PPARγ thereby inducing the [[transcription]] of genes containing the PPARγ [[response element]]. In consequence of this action, 15-deoxy-Δ12,14-PGJ2 causes cells to engage the pathway of [[Programmed cell death]] termed [[Paraptosis]], a form of cell suicide that differs from [[apoptosis]] by involving cytoplasmic vacuolization and mitochondrial swelling rather than plasma membrane blebbing, nuclear condensation and fragmentation, and apoptotic bodies. 15-Deoxy-Δ12,14-PGG2's activation of PPARγ and the induction of paraptosis is responsible for inhibiting the growth of cultured human breast, colon, prostate, and perhaps other cancer cell lines.<ref name="pmid11301410">{{cite journal | vauthors = Straus DS, Glass CK | title = Cyclopentenone prostaglandins: new insights on biological activities and cellular targets | journal = Medicinal Research Reviews | volume = 21 | issue = 3 | pages = 185–210 | year = 2001 | pmid = 11301410 | doi = | url = }}</ref><ref name="pmid26011133">{{cite journal | vauthors = Shibata T | title = 15-Deoxy-Δ¹²,¹⁴-prostaglandin J₂ as an electrophilic mediator | journal = Bioscience, Biotechnology, and Biochemistry | volume = 79 | issue = 7 | pages = 1044–9 | year = 2015 | pmid = 26011133 | doi = 10.1080/09168451.2015.1012149 | url = }}</ref> |
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===Covalent modification of proteins=== |
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The electorphil centers of the three PGJ2's can directly form [[covalent bond]]s with the exposed nucleophilic centers, primarily sulfur residues, of proteins. Again, 15-deoxy-Δ12,14-PGJ2 shows the greatest reactivity and has been the focus of these studies. 15-deoxy-Δ12,14-PGJ2 forms an [[adduct]] with and thereby inactivates [[IκB kinase]]. This works to retain [[NFκB]] in the cell cytoplasm and inhibit its function as a nuclear transcription factor (refer to [[IkB kinase]].<ref name="pmid21843512">{{cite journal | vauthors = Surh YJ, Na HK, Park JM, Lee HN, Kim W, Yoon IS, Kim DD | title = 15-Deoxy-Δ¹²,¹⁴-prostaglandin J₂, an electrophilic lipid mediator of anti-inflammatory and pro-resolving signaling | journal = Biochemical Pharmacology | volume = 82 | issue = 10 | pages = 1335–51 | year = 2011 | pmid = 21843512 | doi = 10.1016/j.bcp.2011.07.100 | url = }}</ref> |
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The [[electrophilic]] centers in the cyclopentenone ring of cylopentenone PGs form [[covalent bond]]s with exposed [[nucleophilic]] centers, primarily the sulfur atom in the thiol residues of [[cysteine]] residues, in a wide range of proteins. This results in the addition of the PG to the protein by a [[Michael addition]] reaction and important modifications in the activity of target proteins that have key functions in cells. 15-Deoxy-Δ12,14-PGJ2 shows the greatest reactivity and has been the focus of these studies. 15-deoxy-Δ12,14-PGJ2 forms [[adduct]]s with the following cellular proteins: |
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*IKK-β subunit of [[IκB kinase]]: IκB serves to retain [[NFκB]] in the cell cytoplasm thereby inhibiting it from entering the nucleus and acting as a [[transcription factor]] (see [[IkB kinase]]) to induce the transcription of genes, many of which contribute to regulating inflammatory responses.<ref name="pmid21843512">{{cite journal | vauthors = Surh YJ, Na HK, Park JM, Lee HN, Kim W, Yoon IS, Kim DD | title = 15-Deoxy-Δ¹²,¹⁴-prostaglandin J₂, an electrophilic lipid mediator of anti-inflammatory and pro-resolving signaling | journal = Biochemical Pharmacology | volume = 82 | issue = 10 | pages = 1335–51 | year = 2011 | pmid = 21843512 | doi = 10.1016/j.bcp.2011.07.100 | url = }}</ref> 15-deoxy-Δ12,14-PGJ2 forms an adduct with the IKK-β subunit of IκB kinase thereby inhibiting the kinases activity thereby promoting the entry of NFκB into the nucleus and stimulating the transcription of more than 15O proteins many of which regulate inflammatory responses. The net effect of this inhibition is to inhibit and/or refers inflammation.<ref name="pmid21843512">{{cite journal | vauthors = Surh YJ, Na HK, Park JM, Lee HN, Kim W, Yoon IS, Kim DD | title = 15-Deoxy-Δ¹²,¹⁴-prostaglandin J₂, an electrophilic lipid mediator of anti-inflammatory and pro-resolving signaling | journal = Biochemical Pharmacology | volume = 82 | issue = 10 | pages = 1335–51 | year = 2011 | pmid = 21843512 | doi = 10.1016/j.bcp.2011.07.100 | url = }}</ref><ref name="pmid10638762">{{cite journal | vauthors = Rossi A, Kapahi P, Natoli G, Takahashi T, Chen Y, Karin M, Santoro MG | title = Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IkappaB kinase | journal = Nature | volume = 403 | issue = 6765 | pages = 103–8 | year = 2000 | pmid = 10638762 | doi = 10.1038/47520 | url = }}</ref><ref name="pmid23049513">{{cite journal | vauthors = Wall SB, Oh JY, Diers AR, Landar A | title = Oxidative modification of proteins: an emerging mechanism of cell signaling | journal = Frontiers in Physiology | volume = 3 | issue = | pages = 369 | year = 2012 | pmid = 23049513 | pmc = 3442266 | doi = 10.3389/fphys.2012.00369 | url = }}</ref> |
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*[[KEAP1]]: cytosolic KEAP1 serves to promote the degradation of [[Nrf2]] by the proteasome thereby inhibiting this transcription factor from entering the nucleus and stimulating the transcription of numerous genes such as [[HMOX1]] which encodes the carbon monoxide-forming and anti-inflammatory protein, HO-1 (see [[Carbon monoxide#Sources]] and [[Carbon monoxide#Normal human physiology]]). 15-deoxy-Δ12,14-PGJ2 forms adducts with KEAP1 cysteines 273 and 288.<ref name="pmid21843512">{{cite journal | vauthors = Surh YJ, Na HK, Park JM, Lee HN, Kim W, Yoon IS, Kim DD | title = 15-Deoxy-Δ¹²,¹⁴-prostaglandin J₂, an electrophilic lipid mediator of anti-inflammatory and pro-resolving signaling | journal = Biochemical Pharmacology | volume = 82 | issue = 10 | pages = 1335–51 | year = 2011 | pmid = 21843512 | doi = 10.1016/j.bcp.2011.07.100 | url = }}</ref><ref name="pmid23049513">{{cite journal | vauthors = Wall SB, Oh JY, Diers AR, Landar A | title = Oxidative modification of proteins: an emerging mechanism of cell signaling | journal = Frontiers in Physiology | volume = 3 | issue = | pages = 369 | year = 2012 | pmid = 23049513 | pmc = 3442266 | doi = 10.3389/fphys.2012.00369 | url = }}</ref> |
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==Activities== |
==Activities== |
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Revision as of 14:09, 21 October 2016
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Cyclopentenone prostaglandins are a subset of prostaglandins or prostenoids (see eicosanoid#classic eicosanoids and eicosanoid#nonclassic eicosanoids) that has 15-deoxy-Δ12,14-prostaglandin J2 (15-d-Δ12,14-PGJ2), Δ12-PGJ2, and PGJ2 as its most prominent members but also including PGA2, PGA1, and, while not classified as such, other PGs. 15-d-Δ12,14-PGJ2, Δ12-PGJ2, and PGJ2 share a common mono-unsaturated cyclopentenone structure as well as a set of similar biological activities including the ability to suppress inflammation responses and the growth as well as survival of cells, particularly those of cancerous or neurological origin. Consequently, these three cyclopentenone-PGs are suggested to be models for the development of novel anti-inflammatory and anti-cancer drugs.
Biochemistry
In cells, COX-1 and COX-2 metabolize arachidonic acid to PGH2 which is then converted to PGE2 by any one of three isozymes, PTGES, PTGES2, and PTGES3 or, alternatively, to PGD2 by either of two enzymes, a glutathione-independent synthase termed lipocalin-type Prostaglandin D2 synthase (PTGDS or L-PGDS) and a glutathione-dependent hematopoietic-type H-PGDS or PTGDS2; the COX's also metabolizes dihomo-gamma-linolenic acid to PGH1 which is metabolized by one of the three PTGES isomzymes to PGE1 (see eicosanoid#Prostanoid pathways). PGE2, PGE1, and PGD2 undergo a dehydration reaction PGA2, PGA1, and PGJ2, respectively. PGD2 conversions form the most studied cyclopentenone PGs. These conversions are as follows:[1][2][3]
- PGD2 is a 20 carbon arachidonic acid metabolite with double bonds between carbons 5,6 and 13,14, a carbon-carbon bond between carbons 8 and 12 (which establishes its cyclopentanone structure), hydroxyl residues attached to carbons 9 and 15, and a ketol residue attached to carbon 11.
- PGD2 undergoes a dehydration reaction (i.e. removal of H2O) across 9-hydroxyl-carbon 10 to form a new 9,10 double bond and thus becomes PGJ2 with a cyclopentenone ring replacing the cyclopentanone ring. Carbon 9 thereby becomes chemically reactive as an electrophilic center.
- PGJ2 undergoes an isomerization reaction in which the carbon 13,14 double bound shifts to the carbon 12,13 position thus becoming Δ12-PGJ2 with a second electrophilic center site at carbon 13.
- Δ12-PGJ2 undergoes a dehydration reaction across 15-hydroxyl-carbon 14 to form a new double bound between carbons 14 and 15 to thereby become 15-deoxy-Δ12,14-PGJ2 with retained electrophile acceptor sites at carbons 9 and 13.
PGE2 and PGE1 are 20 carbon metabolites of arachidonic acid and dihomo-γ-linolenic acid, respectively, with a double bond between carbons 13 and 14, a carbon-carbon bond between carbons 8 and 12 (which establishes their cyclopentanone structure), hydroxyl residues at carbons 11 and 15, and a ketol residue at carbon 9. They differ in that PGE2 has, while PGE1 lacks, a double bound between carbons 5 and 6. Both PGs undergo a dehydration reaction across 11-hydroxyl-carbon 10 to form a new double bond between carbons 10 and 11 thereby becoming PGA2 and PGA1, respectively, with a cyclopenenone ring replacing the cyclopentaonon ring and a newly established electrophilic center site at carbon 11.[2]
The cyclopentenone structures of PGA2 and PGA1 but more particularly of PGJ2, Δ12-PGJ2, and 15-d-Δ12,14-PGJ2 possess α,β-unsaturated carbonyl groups (see Carbonyl group#α,β-Unsaturated carbonyl compounds which serve to establishe high levels of chemical reactivity at nearby carbons 9, 11, and/or 13. These carbons are electrophiles that readily form covalent bonds by Michael reactions acting on exposed nucleophile sites, such as the thiol residues, of diverse proteins. The reaction inactivates or reduces the activity of various functionally important bioactive proteins and is one mechanism by which cylopentenone PGs influence cell function.[1][2][4]
All of the reactions undergone by the above cited PGs occur spontaneously (i.e. are enzyme-independent) in aqueous media. This biochemistry sets very important limitations on the study of the cyclopentenone PGs and to a lesser extent on PGE2, PGE1, and PGD2: a) detection of the cyclopentenone PGs in tissues may and has often reflected their formation during tissue preparation; b) detection of PGE2, PGE1, and PGD2 in tissues may be underestimated because of losses due to their conversion to cyclopentenone PGs; and c) the activities, as studied in vitro or in vivo, of PGJ2 may reflect its conversion to Δ12-PGJ2 or 15-deoxy-Δ12,14-PGJ2, those of Δ12-PGJ2 may reflect its conversion to 15-deoxy-Δ12,14-PGJ2, and those of PGE2, PGE1, or PGD2 may reflect their conversion to any of the cyclopentenone PGs.[1][2]
Mechanisms of action
G protein coupled receptors
The PGJ2 series of cyclopentenone PGs bind to and activate the G protein-coupled receptor, Prostaglandin DP2 receptor, with 15-deoxy-Δ12,14-PGJ2 and PDJ2 exhibiting potencies comparable to PGD2 (i.e. Ki equilibrium constants ~20-45 nanomolar) and Δ12-PGJ2 having 10-fold lesser potency, at least on mouse DP2 receptor.[5][6] These PGJ2's also bind and activate a second G protein-coupled receptor, Prostaglandin DP1 receptor, but require high concentrations to do so; this activation is not considered physiological.[6] DP2 and DP1 are G protein-coupled receptors, with the DP2 receptor coupled to Gi alpha subunit-dependent depression of cellular cAMP levels and causing the potentiation cell injury in neural tissue cultures and with the DP1 receptor coupled to Gs alpha subunit-dependent increases in celluar cAMP levels and the suppression of cell injury in neural tissue cultures.[6]
Peroxisome proliferator-activated receptor gamma
PGD2, PGJ2, Δ12-PGJ2, and 15-deoxy-Δ12,14-PGJ2 activate the transcription factor, PPARγ, with 15-deoxy-Δ12,14-PGJ2 being the most potent of the four PGs.[7] Accordingly, further studies have focused on 15-deoxy-Δ12,14-PGJ2. This PG directly binds with and activates PPARγ thereby inducing the transcription of genes containing the PPARγ response element. In consequence of this action, 15-deoxy-Δ12,14-PGJ2 causes cells to engage the pathway of Programmed cell death termed Paraptosis, a form of cell suicide that differs from apoptosis by involving cytoplasmic vacuolization and mitochondrial swelling rather than plasma membrane blebbing, nuclear condensation and fragmentation, and apoptotic bodies. 15-Deoxy-Δ12,14-PGG2's activation of PPARγ and the induction of paraptosis is responsible for inhibiting the growth of cultured human breast, colon, prostate, and perhaps other cancer cell lines.[2][4]
Covalent modification of proteins
The electrophilic centers in the cyclopentenone ring of cylopentenone PGs form covalent bonds with exposed nucleophilic centers, primarily the sulfur atom in the thiol residues of cysteine residues, in a wide range of proteins. This results in the addition of the PG to the protein by a Michael addition reaction and important modifications in the activity of target proteins that have key functions in cells. 15-Deoxy-Δ12,14-PGJ2 shows the greatest reactivity and has been the focus of these studies. 15-deoxy-Δ12,14-PGJ2 forms adducts with the following cellular proteins:
- IKK-β subunit of IκB kinase: IκB serves to retain NFκB in the cell cytoplasm thereby inhibiting it from entering the nucleus and acting as a transcription factor (see IkB kinase) to induce the transcription of genes, many of which contribute to regulating inflammatory responses.[1] 15-deoxy-Δ12,14-PGJ2 forms an adduct with the IKK-β subunit of IκB kinase thereby inhibiting the kinases activity thereby promoting the entry of NFκB into the nucleus and stimulating the transcription of more than 15O proteins many of which regulate inflammatory responses. The net effect of this inhibition is to inhibit and/or refers inflammation.[1][8][9]
- KEAP1: cytosolic KEAP1 serves to promote the degradation of Nrf2 by the proteasome thereby inhibiting this transcription factor from entering the nucleus and stimulating the transcription of numerous genes such as HMOX1 which encodes the carbon monoxide-forming and anti-inflammatory protein, HO-1 (see Carbon monoxide#Sources and Carbon monoxide#Normal human physiology). 15-deoxy-Δ12,14-PGJ2 forms adducts with KEAP1 cysteines 273 and 288.[1][9]
Activities
The cyclopentenone prostaglandin known as 15d-PGJ2 has been shown to inhibit a gene in T cells which is active in inflammation, such as in various autoimmune diseases.[10][11] 15d-PGJ2 is also demonstrated to suppress hair growth and is implicated in male pattern baldness.[12]
The reactions
References
- ^ a b c d e f Surh YJ, Na HK, Park JM, Lee HN, Kim W, Yoon IS, Kim DD (2011). "15-Deoxy-Δ¹²,¹⁴-prostaglandin J₂, an electrophilic lipid mediator of anti-inflammatory and pro-resolving signaling". Biochemical Pharmacology. 82 (10): 1335–51. doi:10.1016/j.bcp.2011.07.100. PMID 21843512.
- ^ a b c d e Straus DS, Glass CK (2001). "Cyclopentenone prostaglandins: new insights on biological activities and cellular targets". Medicinal Research Reviews. 21 (3): 185–210. PMID 11301410.
- ^ Rossitto M, Ujjan S, Poulat F, Boizet-Bonhoure B (2015). "Multiple roles of the prostaglandin D2 signaling pathway in reproduction". Reproduction (Cambridge, England). 149 (1): R49–58. doi:10.1530/REP-14-0381. PMID 25269616.
- ^ a b Shibata T (2015). "15-Deoxy-Δ¹²,¹⁴-prostaglandin J₂ as an electrophilic mediator". Bioscience, Biotechnology, and Biochemistry. 79 (7): 1044–9. doi:10.1080/09168451.2015.1012149. PMID 26011133.
- ^ Hata AN, Zent R, Breyer MD, Breyer RM (2003). "Expression and molecular pharmacology of the mouse CRTH2 receptor". The Journal of Pharmacology and Experimental Therapeutics. 306 (2): 463–70. doi:10.1124/jpet.103.050955. PMID 12721327.
- ^ a b c Bégué P, Quinet B, Baron S, Challier P, Fontaine JL, Lasfargues G (1989). "[Clinical and pharmacokinetic study of imipenem/cilastatin in children and newborn infants]". Pathologie-biologie. 37 (5): 485–90. PMID 2674874.
- ^ Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, Evans RM (1995). "15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma". Cell. 83 (5): 803–12. PMID 8521497.
- ^ Rossi A, Kapahi P, Natoli G, Takahashi T, Chen Y, Karin M, Santoro MG (2000). "Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IkappaB kinase". Nature. 403 (6765): 103–8. doi:10.1038/47520. PMID 10638762.
- ^ a b Wall SB, Oh JY, Diers AR, Landar A (2012). "Oxidative modification of proteins: an emerging mechanism of cell signaling". Frontiers in Physiology. 3: 369. doi:10.3389/fphys.2012.00369. PMC 3442266. PMID 23049513.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Fionda, C., et al. (2007). Inhibition of Trail gene expression by cyclopentenonic prostaglandin 15-Deoxy-Δ12,14-Prostaglandin J2 in T lymphocytes. Molecular Pharmacology 72:5 1246-57.
- ^ Cernuda-Morollón, E., et al. (2001). 15-Deoxy-Δ12,14-prostaglandin J2 Inhibition of NF-κB-DNA binding through covalent modification of the p50 subunit. Journal of Biological Chemistry 276 35530-36.
- ^ University of Pennsylvania School of Medicine (22 March 2012). "Research identifies inhibitor causing male pattern baldness and target for hair-loss treatments". Retrieved 23 March 2012.