Preferential formation of 8-epi-prostaglandin f2α via the corresponding endoperoxide by a biomimetic cyclization

Corey, E. J.; Shih, Chuan; Shih, Neng‐Yang; Shimoji, Katsuichi

doi:10.1016/s0040-4039(01)91105-0

Cited by 72 publications

(43 citation statements)

References 6 publications

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“…The formation of 8-epi-PGF2,A as a prostaglandin was recently demonstrated by the activity of platelet PGHS-1 in response to collagen, thrombin and AA (Pratico et al, 1995). This is consistent with the biomimetic schema proposed by Corey et al (1984).…”

Section: Discussionsupporting

confidence: 85%

Induction of prostaglandin endoperoxide synthase‐2 in human monocytes associated with cyclo‐oxygenase‐dependent F₂‐isoprostane formation

Patrignani

Santini

Panara

et al. 1996

British J Pharmacology

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1 The isoprostane 8-epi-prostaglandin (PG)F2a is produced by free radical-catalyzed peroxidation of arachidonic acid. It may also be formed as a minor product of the cyclo-oxygenase activity of platelet PGH synthase (PGHS)-l. We investigated 8-epi-PGF2. production associated with induction of the human monocyte PGHS-2 and its pharmacological modulation. 2 Heparinized whole blood samples were drawn from healthy volunteers, 48 h following oral dosing with aspirin 300 mg to suppress platelet cyclo-oxygenase activity. One ml aliquots were incubated with lipopolysaccharide (LPS: 0.1-50 ug ml-') for 0-24 h at 37'C. PGE2 and 8-epi-PGF2a were measured in separated plasma by radioimmunoassay and enzyme immunoassay techniques. 3 Levels of both eicosanoids were undetectable (i.e. <60 pg ml-') at time 0. LPS induced the formation of PGE2 and 8-epi-PGF2, in a time-and concentration-dependent fashion, coincident with the induction of PGHS-2 detected by Western blot analysis of monocyte lysates. After 24 h at 10 mig ml-' LPS, immunoreactive PGE2 and 8-epi-PGF2, averaged 10,480+4,643 and 295+ 140 pg ml-' (mean + s.d., n = 6), respectively. 4 Dexamethasone-and 5-methanesulphonamido-6-(2,4-difluorothiophenyl)-l-indanone (L-745,337), a selective inhibitor of the cyclo-oxygenase activity of PGHS-2, reduced PGE2 and 8-epi-PGF2. production in response to LPS.5 Isolated monocytes produced PGE2 and 8-epi-PGF2, in response to LPS (10 Mg ml-') in a timedependent fashion. Monocyte PGE2 and 8-epi-PGF2a production was largely prevented by dexamethasone (2 gM) and cycloheximide (10 Mg ml-') in association with suppression of PGHS-2 but not of PGHS-1 expression. 6 We conclude that the induction of PGHS-2 in human monocytes is associated with cyclo-oxygenasedependent generation of the vasoconstrictor and platelet-agonist 8-epi-PGF2,.

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Section: Discussionsupporting

confidence: 85%

Induction of prostaglandin endoperoxide synthase‐2 in human monocytes associated with cyclo‐oxygenase‐dependent F₂‐isoprostane formation

Patrignani

Santini

Panara

et al. 1996

British J Pharmacology

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“…Thus, nonregioselective hydrogen atom abstraction from the 7, 10, and 13 positions of an arachidonyl ester produces three regioisomeric pentadienyl radicals. These then react with molecular oxygen to afford four regioisomeric peroxyeicosatetraenoyl radicals that undergo peroxy radical cyclization (28,52) to deliver four structurally isomeric endoperoxides. Besides the geometrically enforced cis relationship of the endoperoxide oxygens and a preference for peroxy radical cyclization to produce stereoisomers with cis disposed side chains (28), each structurally isomeric endoperoxide is expected to be generated as a mixture of 16 stereoisomers that are referred to collectively as isoPGH 2 or iso[n]PGH 2 where [n] specifies the number of carbon atoms in the carboxyl side chain of the non-prostanoid structural isomers.…”

Section: Discussionmentioning

confidence: 99%

Protein Adducts of Iso[4]levuglandin E2, a Product of the Isoprostane Pathway, in Oxidized Low Density Lipoprotein

Salomon

Wang

Brame

et al. 1999

Journal of Biological Chemistry

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Levuglandin (LG) E 2 , a cytotoxic seco prostanoic acid co-generated with prostaglandins by nonenzymatic rearrangements of the cyclooxygenase-derived endoperoxide, prostaglandin H 2 , avidly binds to proteins. That LGE 2 -protein adducts can also be generated nonenzymatically is demonstrated by their production during free radical-induced oxidation of low density lipoprotein (LDL). Like oxidized LDL, LGE 2 -LDL, but not native LDL, undergoes receptor-mediated uptake and impaired processing by macrophage cells. Since radicalinduced lipid oxidation produces isomers of prostaglandins, isoprostanes (isoPs), via endoperoxide intermediates, we postulated previously that a similar family of LG isomers, isoLGs, is cogenerated with isoPs. Now iso[4]LGE 2 -protein epitopes produced by radicalinduced oxidation of arachidonic acid in the presence of protein were detected with an enzyme-linked immunosorbent assay. Iso[4]LGE 2 -protein epitopes are also generated during free radical-induced oxidation of LDL. All of the LGE 2 isomers generated upon oxidation of LDL are efficiently sequestered by covalent adduction with LDL-based amino groups. The potent electrophilic reactivity of iso-LGs can be anticipated to have biological consequences beyond their obvious potential as markers for specific arachidonate-derived protein modifications that may be of value for the quantitative assessment of oxidative injury.

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“…At this stage formation of 8-iso-PGHz, the only product formed in the biomimetic endoperoxide reaction (cf. [42]), is possible. 6 is partly trapped under kinetic control by molecular oxygen followed by H atom abstraction and formation of the corresponding hydroperoxide [R].…”

Section: Discussionmentioning

confidence: 99%

Identification of novel arachidonic acid metabolites formed by prostaglandin H synthase

et al. 1987

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The metabolism of [l-14C]arachidonic acid by microsomal and purified prostaglandin (PG) H synthase was investigated, HPLC analysis confirmed that arachidonic acid (20 : 4) was extensively converted into prostaglandin Gz (PGGz) and/or prostaglandin H 2 (PGHz) but several minor labelled products were formed in addition. Their formation, mediated by PGH synthase was established by inhibition with aspirin and indomethacin [Hecker, M., Hatzelmann, A. & Ullrich, V. (1987) Biochem. Pharmacol. 36, 851 -8551. Upon comparison with authentic reference material these unknown PGH synthase metabolites were identified with respect to chromatographic properties, ultraviolet spectroscopy and mass spectrometry as 11 (R)-hydroperoxy-5Z,8Z,12E,14Z-eicosatetraenoic acid (1 1-00H-20: 4), 12(S)-hydroperoxy-5Z,8E,1OE-heptadecatrienoic acid (00H-17 : 3), 12(S)-hydroxy-SZ,8E,lOE-heptadecatrienoic acid (OH-I 7: 3), 1 S(RS)-hydroperoxy-SZ,8Z,I lZ,13E-eicosatetraenoic acid (1 5-00H-20 : 4), 1 5(RS)-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (1 5-OH-20 : 4), 13-hydroxy-5Z,14Z-prostaglandin HZ, 15(S)-hydroxy-8-iso-5Z,13E-prostaglandin H 2 and 15-0x0-prostaglandin H2. Unlike PGGz and PGHz, S-iso-PGHz, 13-hydroxy-PGHz and 1 5-0x0-PGHz failed to induce aggregation of washed human platelets and to form thromboxane upon incubation with homogeneous human platelet thromboxane synthase. In contrast to the formation of 00H-17:3, 15-0x0-PGHz and OH-17:3 which can be attributed to the heme-catalyzed decomposition of PGGz and PGHz, 11-00H-20: 4,15-(0)OH-20: 4-, 8 iso-PGH2 and 13-hydroxy-PGHz represent potential side products of arachidonic acid conversion into PG endoperoxides. Their formation allows to conclude on PGH synthase mechanism and its intermediates for which an extended reaction scheme is proposed.

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Preferential formation of 8-epi-prostaglandin f2α via the corresponding endoperoxide by a biomimetic cyclization

Cited by 72 publications

References 6 publications

Induction of prostaglandin endoperoxide synthase‐2 in human monocytes associated with cyclo‐oxygenase‐dependent F₂‐isoprostane formation

Induction of prostaglandin endoperoxide synthase‐2 in human monocytes associated with cyclo‐oxygenase‐dependent F₂‐isoprostane formation

Protein Adducts of Iso[4]levuglandin E2, a Product of the Isoprostane Pathway, in Oxidized Low Density Lipoprotein

Identification of novel arachidonic acid metabolites formed by prostaglandin H synthase

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Preferential formation of 8-epi-prostaglandin f2α via the corresponding endoperoxide by a biomimetic cyclization

Cited by 72 publications

References 6 publications

Induction of prostaglandin endoperoxide synthase‐2 in human monocytes associated with cyclo‐oxygenase‐dependent F2‐isoprostane formation

Induction of prostaglandin endoperoxide synthase‐2 in human monocytes associated with cyclo‐oxygenase‐dependent F2‐isoprostane formation

Protein Adducts of Iso[4]levuglandin E2, a Product of the Isoprostane Pathway, in Oxidized Low Density Lipoprotein

Identification of novel arachidonic acid metabolites formed by prostaglandin H synthase

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Induction of prostaglandin endoperoxide synthase‐2 in human monocytes associated with cyclo‐oxygenase‐dependent F₂‐isoprostane formation

Induction of prostaglandin endoperoxide synthase‐2 in human monocytes associated with cyclo‐oxygenase‐dependent F₂‐isoprostane formation