Cellular Uptake and Nuclear Accumulation of Prostaglandin A and J, a Mechanism of Prostaglandin-Induced Growth Inhibition

Narumiya, Shuh; Ohno, Kouji; Fukushima, Masanori; Fujiwara, Maki

doi:10.1007/978-3-642-71904-2_8

Cited by 32 publications

(48 citation statements)

References 15 publications

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“…Several considerations have been made to reconcile these discrepancies. First, it is known that cyPG accumulate inside cells, particularly in cell nuclei (35); therefore, concentrations measured in the culture medium would be expected to be lower than those present intracellularly. Second, cyPG readily form adducts with glutathione or proteins.…”

Section: D-pgj 2 Binds To Cysteine 269 Of C-jun-to Identify the Sitmentioning

confidence: 99%

Molecular Basis for the Direct Inhibition of AP-1 DNA Binding by 15-Deoxy-Δ12,14-prostaglandin J2

Pérez‐Sala

Cernuda-Morollón

Cañada

2003

Journal of Biological Chemistry

124

136

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Section: D-pgj 2 Binds To Cysteine 269 Of C-jun-to Identify the Sitmentioning

confidence: 99%

Molecular Basis for the Direct Inhibition of AP-1 DNA Binding by 15-Deoxy-Δ12,14-prostaglandin J2

Pérez‐Sala

Cernuda-Morollón

Cañada

2003

Journal of Biological Chemistry

124

136

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“…CyPG are reactive compounds that possess an ␣,␤-unsaturated carbonyl group in the cyclopentenone ring. This group may react with sulfhydril groups of cysteine residues of proteins by Michael's addition (34)(35)(36). Based on functional evidence, the direct modification of IB kinase (10,11) and the p65 subunit of NF-B (37) by 15d-PGJ 2 have been proposed.…”

Section: Msmentioning

confidence: 99%

The cyclopentenone 15-deoxy-Δ ^12,14 -prostaglandin J ₂ binds to and activates H-Ras

Oliva

Pérez‐Sala²,

Castrillo³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

125

132

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The cyclopentenone 15-deoxy-⌬ 12,14 -prostaglandin J2 (15d-PGJ2) induces cell proliferation and mitogen-activated protein kinase activation. Here, we describe that these effects are mediated by 15d-PGJ 2-elicited H-Ras activation. We demonstrate that this pathway is specific for H-Ras through the formation of a covalent adduct of 15d-PGJ 2 with Cys-184 of H-Ras, but not with N-Ras or K-Ras. Mutation of C184 inhibited H-Ras modification and activation by 15d-PGJ 2, whereas serum-elicited stimulation was not affected. These results describe a mechanism for the activation of the Ras signaling pathway, which results from the chemical modification of H-Ras by formation of a covalent adduct with cyclopentenone prostaglandins.mitogen-activated protein kinase ͉ cell proliferation ͉ posttranslational modification

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“…Cyclopentenone PGs have attracted considerable interest because of their ability to modulate cell proliferation and differentiation. For example, various compounds of the A-and J-series have been shown to inhibit proliferation with a G 1 cell cycle arrest and to induce differentiation (13)(14)(15). The concentrations of compounds required for this activity are frequently in the micromolar range or above.…”

Section: Docosahexaenoic Acid (C22:63 Dha)mentioning

confidence: 99%

Formation of Highly Reactive A-ring and J-ring Isoprostane-like Compounds (A4/J4-neuroprostanes) in Vivo from Docosahexaenoic Acid

Fam

Murphey

Terry

et al. 2002

Journal of Biological Chemistry

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Free radical-initiated oxidant injury and lipid peroxidation have been implicated in a number of neural disorders. Docosahexaenoic acid is the most abundant unsaturated fatty acid in the central nervous system. We have shown previously that this 22-carbon fatty acid can yield, upon oxidation, isoprostane-like compounds termed neuroprostanes, with E/D-type prostane rings (E 4 /D 4 -neuroprostanes). Eicosanoids with E/D-type prostane rings are unstable and dehydrate to cyclopentenone-containing compounds possessing A-type and J-type prostane rings, respectively. We thus explored whether cyclopentenone neuroprostanes (A 4 /J 4 -neuroprostanes) are formed from the dehydration of E 4 /D 4 -neuroprostanes. Indeed, oxidation of docosahexaenoic acid in vitro increased levels of putative A 4 /J 4 -neuroprostanes 64-fold from 88 ؎ 43 to 5463 ؎ 2579 ng/mg docosahexaenoic acid. Chemical approaches and liquid chromatography/electrospray ionization tandem mass spectrometry definitively identified them as A 4 /J 4 -neuroprostanes. We subsequently showed these compounds are formed in significant amounts from a biological source, rat brain synaptosomes. A 4 /J 4 -neuroprostanes increased 13-fold, from a basal level of 89 ؎ 72 ng/mg protein to 1187 ؎ 217 ng/mg (n ‫؍‬ 4), upon oxidation. We also detected these compounds in very large amounts in fresh brain tissue from rats at levels of 97 ؎ 25 ng/g brain tissue (n ‫؍‬ 3) and from humans at levels of 98 ؎ 26 ng/g brain tissue (n ‫؍‬ 5), quantities that are nearly an order of magnitude higher than other classes of neuroprostanes. Because of the fact that A 4 /J 4 -neuroprostanes contain highly reactive cyclopentenone ring structures, it would be predicted that they readily undergo Michael addition with glutathione and adduct covalently to proteins. Indeed, incubation of A 4 /J 4 -neuroprostanes in vitro with excess glutathione resulted in the formation of large amounts of adducts. Thus, these studies have identified novel, highly reactive A/J-ring isoprostanelike compounds that are derived from docosahexaenoic acid in vivo.

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Cellular Uptake and Nuclear Accumulation of Prostaglandin A and J, a Mechanism of Prostaglandin-Induced Growth Inhibition

Cited by 32 publications

References 15 publications

Molecular Basis for the Direct Inhibition of AP-1 DNA Binding by 15-Deoxy-Δ12,14-prostaglandin J2

Molecular Basis for the Direct Inhibition of AP-1 DNA Binding by 15-Deoxy-Δ12,14-prostaglandin J2

The cyclopentenone 15-deoxy-Δ ^12,14 -prostaglandin J ₂ binds to and activates H-Ras

Formation of Highly Reactive A-ring and J-ring Isoprostane-like Compounds (A4/J4-neuroprostanes) in Vivo from Docosahexaenoic Acid

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Cellular Uptake and Nuclear Accumulation of Prostaglandin A and J, a Mechanism of Prostaglandin-Induced Growth Inhibition

Cited by 32 publications

References 15 publications

Molecular Basis for the Direct Inhibition of AP-1 DNA Binding by 15-Deoxy-Δ12,14-prostaglandin J2

Molecular Basis for the Direct Inhibition of AP-1 DNA Binding by 15-Deoxy-Δ12,14-prostaglandin J2

The cyclopentenone 15-deoxy-Δ 12,14 -prostaglandin J 2 binds to and activates H-Ras

Formation of Highly Reactive A-ring and J-ring Isoprostane-like Compounds (A4/J4-neuroprostanes) in Vivo from Docosahexaenoic Acid

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The cyclopentenone 15-deoxy-Δ ^12,14 -prostaglandin J ₂ binds to and activates H-Ras