Abstract
The isoprostanes (IsoPs) are a unique series of prostaglandin-like compounds formed in vivo via a nonenzymatic mechanism involving the free radical-initiated peroxidation of arachidonic acid. This article summarizes our current knowledge of these compounds. Herein, a historical account of their discovery and the mechanism of their formation are described. A specific class of IsoPs, the F2-IsoPs, are stable, robust molecules that can be measured as indices of endogenous oxidant stress. The utility of these molecules as biomarkers and methods by which these compounds can be quantified are discussed. In addition to the F2-IsoPs, isoprostanes with other prostane ring structures as well as oxidation products with furan and dioxolane rings can be generated from arachidonic acid. And, in more recent years, isoprostane-like compounds have been shown to be formed from polyunsaturated fatty acids including eicosapentaenoic acid [C20:5, omega-3], docosahexaenoic acid [C22:6, omega-3], and adrenic acid [C22:4, omega-6]. These findings will be summarized as well.
Highlights
FORMATION OF ISOPS WITH ALTERNATIVE RING STRUCTURESSince the initial discovery of the F2-IsoPs, the laboratories of Roberts and Morrow have shown that the IsoP pathway provides a mechanism for the generation of other classes of IsoPs from arachidonic acid, which differ in regards to the functional groups on the prostane ring
The isoprostanes (IsoPs) are a unique series of prostaglandin-like compounds formed in vivo via a nonenzymatic mechanism involving the free radical-initiated peroxidation of arachidonic acid
One class of oxidation products formed in abundance in vitro and in vivo is the isoprostanes (IsoPs), which were discovered by our laboratory in 1990
Summary
Since the initial discovery of the F2-IsoPs, the laboratories of Roberts and Morrow have shown that the IsoP pathway provides a mechanism for the generation of other classes of IsoPs from arachidonic acid, which differ in regards to the functional groups on the prostane ring. A2/J2-IsoPs are highly reactive electrophiles, which readily form Michael adducts with cellular thiols, including those found on cysteine residues in proteins and GSH [39]. These cyclopentenone IsoPs are rapidly metabolized in vivo by glutathione transferase enzymes to water-soluble modified glutathione conjugates [40]. A series of compounds termed isoketals (IsoKs or isolevuglandins) can be generated via the IsoP pathway and result from opening of the cyclopentane ring [41] These compounds are highly reactive and readily adduct lysine residues on proteins resulting in covalent modification and protein dysfunction and cross-linking
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