Quantification of F-ring isoprostane-like compounds (F4-neuroprostanes) derived from docosahexaenoic acid in vivo in humans by a stable isotope dilution mass spectrometric assay

Musiek, Erik S.; K., Jin; Yin, Huiyong; Zackert, William E.; Terry, Erin; Porter, Ned A.; Montine, Thomas J.; Morrow, Jason D.

doi:10.1016/j.jchromb.2003.10.036

Cited by 70 publications

(51 citation statements)

References 28 publications

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“…F2-isoprostanes and F4-neuroprostanes were measured by gas chromatography with negative ion chemical ionization mass spectrometry as described previously (Musiek et al, 2004).…”

Section: Methodsmentioning

confidence: 99%

“…Because of the significant lipid content of the brain, a sensitive measure of oxidative damage is the level of lipid peroxidation. Accordingly, we measured F2-isoprostanes, which are free radicalgenerated isomers of prostaglandin PGF 2␣ , and F4-neuroprostanes, which are products of docosohexanoic acid oxidation (Musiek et al, 2004) in 12-month-old male cohorts of APPSwe-PS1⌬E9 mice in EP2ϩ/ϩ and Ϫ/Ϫ backgrounds. Both indices of lipid peroxidation were reduced in APPSwe-PS1⌬E9 mice lacking the EP2 receptor, with a significant effect observed for the neuron-specific F4-neuroprostanes ( Fig.…”

Section: Deletion Of the Ep2 Receptor In Appswe-ps1⌬e9 Mice Reduces Lmentioning

confidence: 99%

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Deletion of the Prostaglandin E₂EP2 Receptor Reduces Oxidative Damage and Amyloid Burden in a Model of Alzheimer's Disease

Liang¹,

Wang²,

Hand³

et al. 2005

J. Neurosci.

219

202

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Epidemiological studies demonstrate that chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) in normal aging populations reduces the risk of developing Alzheimer's disease (AD). NSAIDs inhibit the enzymatic activity of cyclooxygenase-1 (COX-1) and inducible COX-2, which catalyze the first committed step in the synthesis of prostaglandins. These studies implicate COX-mediated inflammation as an early and potentially reversible preclinical event; however, the mechanism by which COX activity promotes development of AD has not been determined. Recent studies implicate the prostaglandin E 2 (PGE 2 ) E prostanoid subtype 2 (EP2) receptor in the development of the innate immune response in brain. Here, we report that deletion of the PGE 2 EP2 receptor in the APPSwe-PS1⌬E9 model of familial AD results in marked reductions in lipid peroxidation in aging mice. This reduction in oxidative stress is associated with significant decreases in levels of amyloid-␤ (A␤) 40 and 42 peptides and amyloid deposition. Aged APPSwe-PS1⌬E9 mice lacking the EP2 receptor harbor lower levels of ␤ C-terminal fragments, the product of ␤-site APP cleaving enzyme (BACE1) processing of amyloid precursor protein. Increases in BACE1 processing have been demonstrated in models of aging and AD and after oxidative stress. Our results indicate that PGE 2 signaling via the EP2 receptor promotes age-dependent oxidative damage and increased A␤ peptide burden in this model of AD, possibly via effects on BACE1 activity. Our findings identify EP2 receptor signaling as a novel proinflammatory and proamyloidogenic pathway in this model of AD, and suggest a rationale for development of therapeutics targeting the EP2 receptor in neuroinflammatory diseases such as AD.

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“…F2-isoprostanes and F4-neuroprostanes were measured by gas chromatography with negative ion chemical ionization mass spectrometry as described previously (Musiek et al, 2004).…”

Section: Methodsmentioning

confidence: 99%

Section: Deletion Of the Ep2 Receptor In Appswe-ps1⌬e9 Mice Reduces Lmentioning

confidence: 99%

Deletion of the Prostaglandin E₂EP2 Receptor Reduces Oxidative Damage and Amyloid Burden in a Model of Alzheimer's Disease

Liang¹,

Wang²,

Hand³

et al. 2005

J. Neurosci.

219

202

View full text Add to dashboard Cite

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“…Quantification of Neuroprostanes-F4-neuroprostanes and F2-isoprostanes were hydrolyzed and purified from the neocortex and quantified by gas chromatography/mass spectrometry as previously described (22,23).…”

Section: Chemicals and Reagents-(rrr)-␣-tocopherolmentioning

confidence: 99%

Prolonged α-Tocopherol Deficiency Decreases Oxidative Stress and Unmasks α-Tocopherol-dependent Regulation of Mitochondrial Function in the Brain

Cuddihy

Ali

Musiek

et al. 2008

Journal of Biological Chemistry

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Vitamin E is the major lipid-soluble chain-breaking antioxidant in mammals and plays an important role in normal development and physiology. Deficiency (whether dietary or genetic) results in primarily nervous system pathology, including cerebellar neurodegeneration and progressive ataxia (abnormal gait). However, despite the widely acknowledged antioxidant properties of vitamin E, only a few studies have directly correlated levels of reactive oxygen species with vitamin E availability in animal models. We explored the relationship between vitamin E and reactive oxygen species in two mouse models of vitamin E deficiency: dietary deficiency and a genetic model (tocopherol transfer protein, Ttp ؊/؊ mice). Both groups of mice developed nearly complete depletion of ␣-tocopherol (the major tocopherol in vitamin E) in most organs, but not in the brain, which was relatively resistant to loss of ␣-tocopherol. F4-neuroprostanes, an index of lipid peroxidation, were unexpectedly lower in brains of deficient mice compared with controls. In vivo oxidation of dihydroethidium by superoxide radical was also significantly lower in brains of deficient animals. Superoxide production by brain mitochondria isolated from vitamin E-deficient and Ttp ؊/؊ mice, measured by electron paramagnetic resonance spectroscopy, demonstrated a biphasic dependence on exogenously added ␣-tocopherol. At low concentrations, ␣-tocopherol enhanced superoxide flux from mitochondria, a response that was reversed at higher concentrations. Here we propose a mechanism, supported by molecular modeling, to explain decreased superoxide production during ␣-tocopherol deficiency and speculate that this could be a beneficial response under conditions of ␣-tocopherol deficiency.␣-Tocopherol was first discovered as a micronutrient indispensable for reproduction in female rats (1). The view that ␣-tocopherol functions solely as a chain-breaking antioxidant has prevailed, reflecting a large body of accumulated experimental evidence showing that ␣-tocopherol can reduce lipid peroxidation in many models and the observation that ␣-tocopherol inhibits lipid peroxidation by scavenging peroxyl radicals faster (10 6 M Ϫ1 s Ϫ1 ) than they can react with other lipids (ϳ10 2 M Ϫ1 s Ϫ1 ) or proteins (2). Recently, however, a broad array of "nonantioxidant" cellular functions for ␣-tocopherol have emerged (reviewed in Refs. 3-8, but see Ref. 9 for the opposing view that supports a pure antioxidative function for ␣-tocopherol). The mechanism by which these "nonantioxidant" actions factor into the observed biological effects of ␣-tocopherol is not yet known. A systematic study of the relationship between levels of ␣-tocopherol and ROS 4 production is one approach to begin to differentiate the documented ability of ␣-tocopherol to act as a lipid peroxidation inhibitor and antioxidant versus its other potential activities in vivo.In the current study, we used two mouse models of vitamin E deficiency: 1) dietary deficiency (VED) in C57BL6 mice and 2) a genetic model, ␣-tocopherol tra...

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“…Hydrolysis and solid-phase extraction of liver and plasma iPF 2α -Ⅲ The purification of iPF 2α -Ⅲ from the liver and plasma were performed as described [18,19] with modifications. Briefly, the tissue sample (50-100 mg) was homogenized in 4 ml ice-cold chloroform:methanol (2:1, v/v).…”

Section: Histological Examinationsmentioning

confidence: 99%

Blood F2-isoprostanes are significantly associated with abnormalities of lipid status in rats with steatosis

Zhu¹,

Sun²,

Liu³

et al. 2008

WJG

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Quantification of F-ring isoprostane-like compounds (F4-neuroprostanes) derived from docosahexaenoic acid in vivo in humans by a stable isotope dilution mass spectrometric assay

Cited by 70 publications

References 28 publications

Deletion of the Prostaglandin E₂EP2 Receptor Reduces Oxidative Damage and Amyloid Burden in a Model of Alzheimer's Disease

Deletion of the Prostaglandin E₂EP2 Receptor Reduces Oxidative Damage and Amyloid Burden in a Model of Alzheimer's Disease

Prolonged α-Tocopherol Deficiency Decreases Oxidative Stress and Unmasks α-Tocopherol-dependent Regulation of Mitochondrial Function in the Brain

Blood F2-isoprostanes are significantly associated with abnormalities of lipid status in rats with steatosis

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Quantification of F-ring isoprostane-like compounds (F4-neuroprostanes) derived from docosahexaenoic acid in vivo in humans by a stable isotope dilution mass spectrometric assay

Cited by 70 publications

References 28 publications

Deletion of the Prostaglandin E2EP2 Receptor Reduces Oxidative Damage and Amyloid Burden in a Model of Alzheimer's Disease

Deletion of the Prostaglandin E2EP2 Receptor Reduces Oxidative Damage and Amyloid Burden in a Model of Alzheimer's Disease

Prolonged α-Tocopherol Deficiency Decreases Oxidative Stress and Unmasks α-Tocopherol-dependent Regulation of Mitochondrial Function in the Brain

Blood F2-isoprostanes are significantly associated with abnormalities of lipid status in rats with steatosis

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Product

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Deletion of the Prostaglandin E₂EP2 Receptor Reduces Oxidative Damage and Amyloid Burden in a Model of Alzheimer's Disease

Deletion of the Prostaglandin E₂EP2 Receptor Reduces Oxidative Damage and Amyloid Burden in a Model of Alzheimer's Disease