The Isoprostanes: A Perspective

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

doi:10.1016/s0090-6980(97)00183-4

Cited by 110 publications

(87 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Isoprostanes are chemically stable, free radical-catalyzed products of arachidonic acid (AA) that are structural isomers of conventional prostaglandins 11,12 for which a novel nomenclature 13 has recently been proposed ( Figure 1). We have recently immunolocalized 1 of these compounds, iPF 2␣ -III (formerly known as 8-iso-PGF 2␣ ), to monocyte/macrophages and vascular smooth muscle cells in human atherosclerotic plaque.…”

Section: See P 2785mentioning

confidence: 99%

Increased Formation of Distinct F ₂ Isoprostanes in Hypercholesterolemia

et al. 1998

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

Section: See P 2785mentioning

confidence: 99%

Increased Formation of Distinct F ₂ Isoprostanes in Hypercholesterolemia

et al. 1998

View full text Add to dashboard Cite

show abstract

“…3, revealed that all eight possible isoprostane diastereoisomers were present in the reaction mixture. 2 The fragments detected are the result of Hock fragmentation as described in Ref. 13; the assignment of structure to Ch-11-t, t-HPETE is tentative.…”

Section: Resultsmentioning

confidence: 72%

“…2 shows the UV absorption of the oxidation mixture at 234 nm, a wavelength characteristic of the conjugated diene chromophore. Panel b shows the SRM chromatogram for Ch-15-HPETE, the starting material, whereas detection of Ch-11-t,t-HpETE is shown in panel c. 2 Formation of Ch-11-t,t-HpETE is consistent with ␤-fragmentation of the 15-peroxyl radical and re-addition of oxygen at C-11 as shown in Scheme 2. An SRM chromatogram of bicyclic endoperoxides is shown in panel d, whereas monocyclic and serial cyclic peroxides are shown in panels e and f, respectively.…”

Section: Resultsmentioning

confidence: 82%

“…In this mechanism, the 15-peroxyl radical undergoes 4-exo cyclization to give a dioxetane intermediate as shown in Scheme 2b. This mechanism has been proposed by Rokach et al (2) and others (17)(18)(19)(20)(21) as an alternative to explain the formation of regioisomeric bicyclic endoperoxides from an arachidonyl-containing lipid.…”

mentioning

confidence: 89%

“…The oxidation products derived from arachidonic acid play an important role in the control of organ physiology (1)(2)(3). The bicyclic endoperoxide prostaglandin G 2 (PGG 2 ) 1 is formed from the oxidation of arachidonic acid by cyclooxygenases (COX enzymes).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Mechanisms for the Formation of Isoprostane Endoperoxides from Arachidonic Acid

Yin¹,

Havrilla²,

Gao

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

The isoprostanes are a class of autoxidation products generated from arachidonic acid (or its esters) by a free radical initiated process. The potent biological activity of these compounds has been attracting intense research interest since they were detected in humans as well as animal models in the early 1990s. The measurement of these compounds has been regarded as one of the most useful non-invasive biomarkers for oxidative stress status. Two mechanisms for the formation of these compounds have been proposed. In the first mechanism, a peroxyl radical undergoes successive 5-exo cyclizations analogous to the enzymatic mechanism proposed for prostaglandin biosynthesis. The second mechanism starts with a 4-exo cyclization of a peroxyl radical leading to an intermediate dioxetane, a mechanism that has also been proposed for prostaglandin biosynthesis as well as for the formation of 4-hydroxy nonenal (HNE). Autoxidation of cholesteryl-15-HpETE under free radical conditions provides Type IV isoprostanes. The "dioxetane" mechanism for isoprostane generation from 15-HpETE requires that optically pure products are formed from an optically pure reactant, whereas an alternate mechanism for the process involving ␤-fragmentation of the 15-peroxyl would give racemic isoprostane products. We have carried out a test of the mechanism based upon these stereochemical requirements. The results of analysis of the product mixture derived from autoxidation of optically pure Ch-15-HpETE by atmospheric pressure chemical ionizationmass spectrometry coupled with chiral high performance liquid chromatography indicate that the major isoprostane diastereomers are formed as a racemic mixture. These experimental results are consistent with a mechanism for isoprostane formation involving ␤-fragmentation of the 15-peroxyl radical followed by re-addition of oxygen to form the 11-HPETE peroxyl, and they exclude a mechanism proceeding through the formation of a dioxetane intermediate.

show abstract

F₂‐Isoprostanes as Markers of Oxidant Stress: An Overview

Musiek

Morrow

2005

CP Toxicology

View full text Add to dashboard Cite

The isoprostanes are a unique series of prostaglandin-like compounds formed in vivo via a non-enzymatic mechanism involving the free radical-initiated peroxidation of arachidonic acid. This unit summarizes selected aspects regarding current knowledge of these compounds and their value as markers of oxidative injury. Novel aspects related to the biochemistry of isoprostane formation are discussed and methods by which these compounds can be analyzed and quantified are summarized. A considerable portion of this unit examines the utility of F(2)-isoprostanes as markers of oxidant injury in vitro and in vivo. Numerous studies carried out over the past decade have shown that these compounds are extremely accurate measures of lipid peroxidation in animals and humans and have illuminated the role of oxidant injury in a number of human diseases.

show abstract

The Isoprostanes: A Perspective

Cited by 110 publications

References 83 publications

Increased Formation of Distinct F ₂ Isoprostanes in Hypercholesterolemia

Increased Formation of Distinct F ₂ Isoprostanes in Hypercholesterolemia

Mechanisms for the Formation of Isoprostane Endoperoxides from Arachidonic Acid

F₂‐Isoprostanes as Markers of Oxidant Stress: An Overview

Contact Info

Product

Resources

About

The Isoprostanes: A Perspective

Cited by 110 publications

References 83 publications

Increased Formation of Distinct F 2 Isoprostanes in Hypercholesterolemia

Increased Formation of Distinct F 2 Isoprostanes in Hypercholesterolemia

Mechanisms for the Formation of Isoprostane Endoperoxides from Arachidonic Acid

F2‐Isoprostanes as Markers of Oxidant Stress: An Overview

Contact Info

Product

Resources

About

Increased Formation of Distinct F ₂ Isoprostanes in Hypercholesterolemia

Increased Formation of Distinct F ₂ Isoprostanes in Hypercholesterolemia

F₂‐Isoprostanes as Markers of Oxidant Stress: An Overview