Dataset Information

Reinterpreting the best biomarker of oxidative stress: The 8-iso-PGF(2?)/PGF(2?) ratio distinguishes chemical from enzymatic lipid peroxidation.

ABSTRACT: The biomarker 8-iso-prostaglandin F2? (8-iso-PGF2?) is regarded as the gold standard for detection of excessive chemical lipid peroxidation in humans. However, biosynthesis of 8-iso-PGF2? via enzymatic lipid peroxidation by prostaglandin-endoperoxide synthases (PGHSs), which are significantly induced in inflammation, could lead to incorrect biomarker interpretation. To resolve the ambiguity with this biomarker, the ratio of 8-iso-PGF2? to prostaglandin F2? (PGF2?) is established as a quantitative measure to distinguish enzymatic from chemical lipid peroxidation in vitro, in animal models, and in humans. Using this method, we find that chemical lipid peroxidation contributes only 3% to the total 8-iso-PGF2? in the plasma of rats. In contrast, the 8-iso-PGF2? levels in plasma of human males are generated >99% by chemical lipid peroxidation. This establishes the potential for an alternate pathway of biomarker synthesis, and draws into question the source of increases in 8-iso-PGF2? seen in many human diseases. In conclusion, increases in 8-iso-PGF2? do not necessarily reflect increases in oxidative stress; therefore, past studies using 8-iso-PGF2? as a marker of oxidative stress may have been misinterpreted. The 8-iso-PGF2?/PGF2? ratio can be used to distinguish biomarker synthesis pathways and thus confirm the potential change in oxidative stress in the myriad of disease and chemical exposures known to induce 8-iso-PGF2?.

SUBMITTER: van 't Erve TJ

PROVIDER: S-EPMC4441846 | biostudies-other | 2015 Jun

REPOSITORIES: biostudies-other

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Reinterpreting the best biomarker of oxidative stress: The 8-iso-PGF(2α)/PGF(2α) ratio distinguishes chemical from enzymatic lipid peroxidation.

van 't Erve Thomas J TJ Lih Fred B FB Kadiiska Maria B MB Deterding Leesa J LJ Eling Thomas E TE Mason Ronald P RP

Free radical biology & medicine 20150312

The biomarker 8-iso-prostaglandin F2α (8-iso-PGF2α) is regarded as the gold standard for detection of excessive chemical lipid peroxidation in humans. However, biosynthesis of 8-iso-PGF2α via enzymatic lipid peroxidation by prostaglandin-endoperoxide synthases (PGHSs), which are significantly induced in inflammation, could lead to incorrect biomarker interpretation. To resolve the ambiguity with this biomarker, the ratio of 8-iso-PGF2α to prostaglandin F2α (PGF2α) is established as a quantitativ ...[more]

PMID: 25772010

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Project description:A new mitochondria-targeted probe MitoCLox was designed as a starting compound for a series of probes sensitive to cardiolipin (CL) peroxidation. Fluorescence microscopy reported selective accumulation of MitoCLox in mitochondria of diverse living cell cultures and its oxidation under stress conditions, particularly those known to cause a selective cardiolipin oxidation. Ratiometric fluorescence measurements using flow cytometry showed a remarkable dependence of the MitoCLox dynamic range on the oxidation of the sample. Specifically, MitoCLox oxidation was induced by low doses of hydrogen peroxide or organic hydroperoxide. The mitochondria-targeted antioxidant 10-(6'-plastoquinonyl)decyltriphenyl-phosphonium (SkQ1), which was shown earlier to selectively protect cardiolipin from oxidation, prevented hydrogen peroxide-induced MitoCLox oxidation in the cells. Concurrent tracing of MitoCLox oxidation and membrane potential changes in response to hydrogen peroxide addition showed that the oxidation of MitoCLox started without a delay and was complete during the first hour, whereas the membrane potential started to decay after 40 minutes of incubation. Hence, MitoCLox could be used for splitting the cell response to oxidative stress into separate steps. Application of MitoCLox revealed heterogeneity of the mitochondrial population; in living endothelial cells, a fraction of small, rounded mitochondria with an increased level of lipid peroxidation were detected near the nucleus. In addition, the MitoCLox staining revealed a specific fraction of cells with an increased level of oxidized lipids also in the culture of human myoblasts. The fraction of such cells increased in high-density cultures. These specific conditions correspond to the initiation of spontaneous myogenesis in vitro, which indicates that oxidation may precede the onset of myogenic differentiation. These data point to a possible participation of oxidized CL in cell signalling and differentiation.

Dataset Information

Reinterpreting the best biomarker of oxidative stress: The 8-iso-PGF(2?)/PGF(2?) ratio distinguishes chemical from enzymatic lipid peroxidation.

Publications

Reinterpreting the best biomarker of oxidative stress: The 8-iso-PGF(2α)/PGF(2α) ratio distinguishes chemical from enzymatic lipid peroxidation.

Similar Datasets

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