Identification of a Novel Class of Endoperoxides from Arachidonate Autoxidation

Yin, Huiyong; Morrow, Jason D.; Porter, Ned A.

doi:10.1074/jbc.m307137200

Cited by 59 publications

(59 citation statements)

References 39 publications

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“…As is evident, the 7-and 17-series are major regioisomers compared with the 14-and 10-series. The formation of dioxolane-isoprostanes from 14-and 10-series isomers may be responsible for the regioselectivity, as in the case of arachidonate oxidation (29). In combination, these structural data from derivatization, CID, and SRM experiments establish that the F 2 -IsoP-like compounds generated from AdA oxidation are F 2 -dihomo-IsoPs.…”

Section: Identification and Quantification Of Unesterified Ada Productsmentioning

confidence: 76%

F2-Dihomo-isoprostanes arise from free radical attack on adrenic acid

VanRollins

Woltjer

Yin

et al. 2008

Journal of Lipid Research

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Unlike F 4 -neuroprostanes (F 4 -NeuroPs), which are relatively selective in vivo markers of oxidative damage to neuronal membranes, there currently is no method to assess the extent of free radical damage to myelin with relative selectively. The polyunsaturated fatty acid adrenic acid (AdA) is susceptible to free radical attack and, at least in primates, is concentrated in myelin within white matter.

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Section: Identification and Quantification Of Unesterified Ada Productsmentioning

confidence: 76%

F2-Dihomo-isoprostanes arise from free radical attack on adrenic acid

VanRollins

Woltjer

Yin

et al. 2008

Journal of Lipid Research

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“…Such regioisomeric predominance has also been reported for F 2 -IsoP regioisomers in which 5-and 15-series compounds are formed in greater abundance than 8-and 12-series molecules (27). At least part of the reason for this is likely due to the fact that precursors of 8-and 12-series F 2 -IsoPs can undergo further oxidation and cyclization to yield a novel class of compounds termed dioxolane endoperoxides (41). Although undetermined at present, it is likely that a similar mechanism may account for the predominance of 5-and 18-series F 3 -IsoPs.…”

Section: Discussionmentioning

confidence: 99%

Formation of F-ring Isoprostane-like Compounds (F3-Isoprostanes) in Vivo from Eicosapentaenoic Acid

Gao¹,

Yin²,

Milne³

et al. 2006

Journal of Biological Chemistry

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116

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Eicosapentaenoic acid (EPA, C20:5, -3) is the most abundant polyunsaturated fatty acid (PUFA) in fish oil. Recent studies suggest that the beneficial effects of fish oil are due, in part, to the generation of various free radical-generated non-enzymatic bioactive oxidation products from -3 PUFAs, although the specific molecular species responsible for these effects have not been identified. Our research group has previously reported that pro-inflammatory prostaglandin F 2 -like compounds, termed F 2 -isoprostanes (IsoPs), are produced in vivo by the free radical-catalyzed peroxidation of arachidonic acid and represent one of the major products resulting from the oxidation of this PUFA. Based on these observations, we questioned whether F 2 -IsoP-like compounds (F 3 -IsoPs) are formed from the oxidation of EPA in vivo. Oxidation of EPA in vitro yielded a series of compounds that were structurally established to be F 3 -IsoPs using a number of chemical and mass spectrometric approaches. The amounts formed were extremely large (up to 8.7 ؉ 1.0 g/mg EPA) and greater than levels of F 2 -IsoPs generated from arachidonic acid. We then examined the formation of F 3 -IsoPs in vivo in mice. Levels of F 3 -IsoPs in tissues such as heart are virtually undetectable at baseline, but supplementation of animals with EPA markedly increases quantities up to 27.4 ؉ 5.6 ng/g of heart. Interestingly, EPA supplementation also markedly reduced levels of pro-inflammatory arachidonate-derived F 2 -IsoPs by up to 64% ( p < 0.05). Our studies provide the first evidence that identify F 3 -IsoPs as novel oxidation products of EPA that are generated in vivo. Further understanding of the biological consequences of F 3 -IsoP formation may provide valuable insights into the cardioprotective mechanism of EPA.

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“…Most of the predicted oxidation products of EPA have cyclic peroxide moieties and are unstable when analyzed by conventional ESI-MS. However, a milder ionization technique, Ag ϩ CIS-MS, has proven to be useful in identification of these intact peroxides based on characteristic fragmentation induced by Ag ϩ coordination of lipids (30,32,33). Furthermore, the doublet peaks in the Ag ϩ CIS spectra are characteristic of silver adducts because silver has two isotopes 107 daltons and 109 daltons with almost equal abundance.…”

Section: Identification Of Intact Peroxides From the Oxidation Of Epamentioning

confidence: 99%

“…As would be predicted based on our unified mechanism of EPA oxidation, six series of F 3 -IsoPs are formed from EPA whereas only four series of F 2 -IsoPs are generated from arachidonic acid. We have previously shown that 5-and 15-series F 2 -IsoPs are formed in greater abundance than 8-and 12-series F 2 -IsoPs because the precursors that lead to 8-and 12-series F 2 -IsoPs can further cyclized to form dioxolaneIsoPs (33). Similarly, we would predict that the oxidation of EPA will lead to the preferential generation of 5-and 18-series F 3 -IsoPs compared with 8-, 12-, 11-, and 15-series compounds because the precursors of the latter F 3 -IsoPs can undergo further oxidation to form dioxolane-IsoPs and bis-dioxolaneIsoPs.…”

Section: Identification Of Novel Oxidation Products From Epa In Vivo-mentioning

confidence: 99%

Identification of Novel Autoxidation Products of the ω-3 Fatty Acid Eicosapentaenoic Acid in Vitro and in Vivo

Yin

Brooks

Gao

et al. 2007

Journal of Biological Chemistry

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Increased intake of fish oil rich in the -3 fatty acids eicosapentaenoic acid (EPA, C20:5 -3) and docosahexaenoic acid (DHA, C22:6 -3) reduces the incidence of human disorders such as atherosclerotic cardiovascular disease. However, mechanisms that contribute to the beneficial effects of fish oil consumption are poorly understood. Mounting evidence suggests that oxidation products of EPA and DHA may be responsible, at least in part, for these benefits. Previously, we have defined the free radical-induced oxidation of arachidonic acid in vitro and in vivo and have proposed a unified mechanism for its peroxidation. We hypothesize that the oxidation of EPA can be rationally defined but would be predicted to be significantly more complex than arachidonate because of the fact that EPA contains an addition carbon-carbon double bond. Herein, we present, for the first time, a unified mechanism for the peroxidation of EPA. Novel oxidation products were identified employing state-ofthe-art mass spectrometric techniques including Ag ؉ coordination ionspray and atmospheric pressure chemical ionization mass spectrometry. Predicted compounds detected both in vitro and in vivo included monocylic peroxides, serial cyclic peroxides, bicyclic endoperoxides, and dioxolane-endoperoxides.

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Identification of a Novel Class of Endoperoxides from Arachidonate Autoxidation

Cited by 59 publications

References 39 publications

F2-Dihomo-isoprostanes arise from free radical attack on adrenic acid

F2-Dihomo-isoprostanes arise from free radical attack on adrenic acid

Formation of F-ring Isoprostane-like Compounds (F3-Isoprostanes) in Vivo from Eicosapentaenoic Acid

Identification of Novel Autoxidation Products of the ω-3 Fatty Acid Eicosapentaenoic Acid in Vitro and in Vivo

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