Total synthesis of a novel isoprostane IPF2α-I and its identification in biological fluids

Adiyaman, Mustafa; Lawson, John A.; Hwang, Sangwon; Khanapure, Subhash P.; FitzGerald, Garret A.; Rokach, Joshua

doi:10.1016/0040-4039(96)00973-2

Cited by 55 publications

(30 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…10) (41). A similar situation has previously been encountered in the metabolism of LTE 4 (34,35,42), which is metabolized by voxidation, followed by two cycles of b-oxidation coupled with reduction of the 14,15-double bond.…”

Section: Discussionmentioning

confidence: 91%

“…If this is true, measurement of iPF 3a -VI could be an excellent index of the combined endogenous autooxidation of EPA and DHA, and might reflect a process of relevance to disease progression in syndromes of neurodegeneration, such as AD. Recently, F 4 -nPs have been detected in brain tissue (19,46). However, the measurement of changes in nP levels in urine as an index of AD has not been successful (20).…”

Section: Discussionmentioning

confidence: 99%

“…We have previously reported on the total synthesis of iPs and metabolites derived from free radical peroxidation of arachidonic acid (AA) (3)(4)(5)(6)(7).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Oxidized derivatives of ω-3 fatty acids: identification of IPF3α-VI in human urine

Lawson

Kim

Powell

et al. 2006

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

Isoprostanes (iPs) are prostaglandin-like molecules derived from autoxidation of polyunsaturated fatty acids (PUFAs). Urinary iP levels have been used as indices of in vivo lipid peroxidation. Thus far, it has only been possible to measure iPs derived from arachidonic acid in urine, because levels of iPs/neuroprostanes (nPs) derived from v3-PUFAs have been found to be below detection limits of available assays. Because of the interest in v3-PUFA dietary supplementation, we developed specific methods to measure nPF 4a -VI and iPF 3a -VI [derived from 4,7,10,13,16,19-docosahexaenoic acid (DHA) and 5,8,11,14,17-eicosapentaenoic acid (EPA)] using a combination of chemical synthesis, gas chromatography/mass spectrometry (GC/MS), and liquid chromatography tandem mass spectrometry (LC/MS/MS). Although nPF 4a -VI was below the detection limit of the assay, we conclusively identified iPF 3a -VI in human urine by GC/MS and LC/MS/MS. The mean levels in 26 subjects were z300 pg/mg creatinine. Our failure to detect nPF 4a -VI may have been due to its rapid metabolism by b-oxidation to iPF 3a -VI, which we showed to occur in rat liver homogenates. In contrast, iPF 3a -VI is highly resistant to b-oxidation in vitro. Thus iPF 3a -VI can be formed by two mechanisms: i) direct autoxidation of EPA, and ii) b-oxidation of nPF 4a -VI, formed by autoxidation of DHA. This iP may therefore serve as an excellent marker for the combined in vivo peroxidation of EPA and DHA.-Lawson, J. A., S. Kim, W. S. Powell, G. A. FitzGerald, and J. Rokach. Oxidized derivatives of v-3 fatty acids: identification of IPF 3a -VI in human urine. J. Lipid Res. 2006Res. . 47: 2515Res. -2524

show abstract

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Oxidized derivatives of ω-3 fatty acids: identification of IPF3α-VI in human urine

Lawson

Kim

Powell

et al. 2006

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…iPF 2␣ -VI is a member of a distinct class of F 2 isoprostanes. 36,37 It is not formed by COX, and its excretion in volunteers is not suppressed by aspirin. Urinary levels of iPF 2␣ -VI are higher than those of iPF 2␣ -III.…”

Section: Discussionmentioning

confidence: 99%

Increased Formation of Distinct F ₂ Isoprostanes in Hypercholesterolemia

et al. 1998

Self Cite

View full text Add to dashboard Cite

Background-F 2 isoprostanes are stable, free radical-catalyzed products of arachidonic acid that reflect lipid peroxidation in vivo. Methods and Results-Specific assays were developed by use of mass spectrometry for the F 2 isoprostanes iPF 2␣ -III and iPF 2␣ -VI and arachidonic acid (AA). Urinary excretion of the 2 F 2 isoprostanes was significantly increased in hypercholesterolemic patients, whereas substrate AA in urine did not differ between the groups. iPF 2␣ -III (pmol/mmol creatinine) was elevated (PϽ0.0005) in homozygous familial hypercholesterolemic (HFH) patients (85Ϯ5.5; nϭ38) compared with age-and sex-matched normocholesterolemic control subjects (58Ϯ4.

show abstract

“…F 2 isoprostanes (iPs) are PGF 2␣ isomers that are generated by free radical-catalyzed peroxidation of arachidonic acid (10). We have performed total stereospecific synthesis of several iPs, including 8,12-iso-iPF 2␣ -III (previously known as 12-iso-PGF 2␣ ) (11) and iPF 2␣ -VI (previously known as IPF 2␣ -I) (12) and have recently demonstrated that the iP, 8,12-iso-iPF 2␣ -III, may activate FP in a specific and saturable manner (13). The iP, 8,12-iso-iPF 2␣ -III is a member of the group III isoprostanes, which also includes 8-iso-iPF 2␣ -III.…”

mentioning

confidence: 99%

Prostaglandin F2α (PGF2α) and the Isoprostane, 8,12-iso-Isoprostane F2α-III, Induce Cardiomyocyte Hypertrophy

Kunapuli¹,

Lawson²,

Rokach³

et al. 1998

Journal of Biological Chemistry

Self Cite

119

View full text Add to dashboard Cite

Prostaglandin receptors may be activated by their cognate ligand or by free radical catalyzed isoprostanes, products of arachidonic acid peroxidation. For example, prostaglandin F 2␣ (PGF 2␣ ) causes hypertrophy of neonatal rat ventricular myocytes, via the PGF 2␣ receptor (FP). However, the FP may also be activated by the isoprostane, 8,12-iso-iPF 2␣ -III (Kunapuli, P., Lawson, J. A., Rokach, J., and FitzGerald, G. A. (1997) J. Biol. Chem. 272, 27147-27154). Both ligands induce myocyte hypertrophy with overlapping potencies. Interestingly, the hypertrophic effects of these two agonists on cardiomyocytes are additive. Furthermore, the preference of these two agonists for activation of intracellular signal transduction pathways differs in several respects. Thus, PGF 2␣ and 8,12-isoiPF 2␣ -III stimulate inositol phosphate formation with EC 50 values of 50 ؎ 12 nM and 3.5 ؎ 0.6 M, respectively. Moreover, PGF 2␣ causes a robust activation (ϳ50-fold) of Erk2, whereas 8,12-iso-iPF 2␣ -III has no effect. Similarly, PGF 2␣ causes translocation of cytosolic phospholipase A 2 and also results in a 7-fold increment in the formation of 6-keto-PGF 1␣ , whereas 8,12-iso-iPF 2␣ -III exerts no effect on this pathway. On the other hand, both agonists are equally potent in activating JNK1 and c-Jun, whereas neither activates the p38 kinase. Both PGF 2␣ and 8,12-isoiPF 2␣ -III activate the p70S6 kinase (p70 S6K ), but not Akt, downstream of phosphatidylinositol-3-kinase (PI3K). However, both wortmannin, a PI3K inhibitor, and rapamycin, an inhibitor of p70 S6K activity, inhibit 8,12-isoiPF 2␣ -III -induced myocyte hypertrophy, with IC 50 values of 60 ؎ 12 and 3 ؎ 1.7 nM, respectively, whereas neither compound abrogates the PGF 2␣ -mediated response. Thus, both PGF 2␣ and 8,12-iso-iPF 2␣ -III induce myocyte hypertrophy via discrete signaling pathways. Although both agonists signal via the JNK pathway to initiate changes in c-Jun-dependent gene transcription, PGF 2␣ preferentially activates the MEK-Erk2-cytosolic phospholipase A 2 pathway. In contrast, the PI3K-p70 S6K pathway appears to be essential for 8,12-iso-iPF 2␣ -III-induced myocyte hypertrophy. Prostaglandins (PGs)1 are arachidonic acid metabolites that are produced in a wide variety of tissues in response to mechanical and chemical stimuli. The actions of PGF 2␣ are thought to be mediated via the PGF 2␣ receptor (FP), which is a member of the G protein-coupled receptor (GPCR) superfamily (1). PGF 2␣ has diverse physiological actions, ranging from being a potent luteolytic agent (2) to causing vascular smooth muscle contraction (3). In the myocardium, the formation of PGs is induced by pressure overload (4) which can result in cardiac hypertrophy (5, 6). Conversely, PG synthase inhibitors diminish the hypertrophic response induced by hypertension (7).Prostaglandin F 2␣ (PGF 2␣ ) has recently been shown to stimulate hypertrophy of neonatal rat ventricular myocytes and to induce the expression of myofibrillar genes, independent of muscle contraction (8). Paoni and co-workers (...

show abstract

Total synthesis of a novel isoprostane IPF2α-I and its identification in biological fluids

Cited by 55 publications

References 13 publications

Oxidized derivatives of ω-3 fatty acids: identification of IPF3α-VI in human urine

Oxidized derivatives of ω-3 fatty acids: identification of IPF3α-VI in human urine

Increased Formation of Distinct F ₂ Isoprostanes in Hypercholesterolemia

Prostaglandin F2α (PGF2α) and the Isoprostane, 8,12-iso-Isoprostane F2α-III, Induce Cardiomyocyte Hypertrophy

Contact Info

Product

Resources

About

Total synthesis of a novel isoprostane IPF2α-I and its identification in biological fluids

Cited by 55 publications

References 13 publications

Oxidized derivatives of ω-3 fatty acids: identification of IPF3α-VI in human urine

Oxidized derivatives of ω-3 fatty acids: identification of IPF3α-VI in human urine

Increased Formation of Distinct F 2 Isoprostanes in Hypercholesterolemia

Prostaglandin F2α (PGF2α) and the Isoprostane, 8,12-iso-Isoprostane F2α-III, Induce Cardiomyocyte Hypertrophy

Contact Info

Product

Resources

About

Increased Formation of Distinct F ₂ Isoprostanes in Hypercholesterolemia