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Urinary prostaglandin F2alpha is generated from the isoprostane pathway and not the cyclooxygenase in humans.

Urinary prostaglandin F2alpha is generated from the isoprostane pathway and not the cyclooxygenase in humans. Research Abstract Details 

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  • Urinary prostaglandin F2alpha is generated from the isoprostane pathway and not the cyclooxygenase in humans. Abstract Text:

    huiyong yinHuiyong Yin,ling gaoLing Gao,hsin-hsiung taiHsin-Hsiung Tai,laine j murpheyLaine J Murphey,ned a porterNed A Porter,jason d morrowJason D Morrow,

    Prostaglandins (PGs) derived from the enzymatic oxidation of arachidonic acid by the cyclooxygenases (COXs) are potent lipid mediators involved in human physiology and pathophysiology. Structurally similar compounds, the isoprostanes (IsoPs), are generated from the free radical-catalyzed oxidation of arachidonic acid independent of COX. IsoPs exhibit significant bioactivity and play a role in the pathogenesis of diseases associated with oxidant injury. As one of the major PGs, prostaglandin F(2alpha) (PGF(2alpha)) is present in human urine in significant concentrations and is presumed to be derived from COX activity. We determined, however, that levels of putative PGF(2alpha) in urine cannot be suppressed by nonsteroidal anti-inflammatory agents, suggesting that it is generated via another mechanism(s). An important difference between COX-derived PGF(2alpha) and the IsoPs is that the former is an optically pure compound, whereas IsoPs are racemic. Utilizing a rodent model of oxidative stress, we now show that significant amounts of compounds identical in all respects to PGF(2alpha) and its enantiomer, ent-PGF(2alpha), are formed in equal amounts esterified in tissue phospholipids, suggesting that these compounds are derived via the IsoP pathway. Further, employing liquid chromatography/mass spectrometry, the vast majority of putative PGF(2alpha) in human urine is derived from the free radical-initiated peroxidation of arachidonate independent of COX and is composed of PGF(2alpha) and its enantiomer, although the latter compound is approximately 2-fold more abundant. Thus, quantification of urinary PGF(2alpha) actually reflects oxidative stress status as opposed to COX activity. Indeed, levels of this compound are elevated in urine from cigarette smokers and in humans with hypercholesterolemia, two conditions associated with oxidant stress. The elucidation that urinary PGF(2alpha) in humans is derived from the IsoP pathway has implications regarding PG formation and inhibition in vivo.

    Urinary prostaglandin F2alpha is generated from the isoprostane pathway and not the cyclooxygenase in humans. Publishing Authors By Initials

    h yinH Yin,l gaoL Gao,hh taiHH Tai,lj murpheyLJ Murphey,na porterNA Porter,jd morrowJD Morrow,

    For similar behavior and behavior mechanisms: behavior: habits: smoking research abstracts see: behavior and behavior mechanisms: behavior: habits: smoking research

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    Urinary prostaglandin F2alpha is generated from the isoprostane pathway and not the cyclooxygenase in humans. Journal Published:

    PUBLICATION TYPE: Research Support, N.I.H., Extr

    Journal: The Journal of biological chemistry

    VOLUME: 282

    Page Numbers: 329-36

    Journal Abbreviation: J. Biol. Chem.

    ISSN: 0021-9258

    DAY: 15

    MONTH: 11

    YEAR: 2006

    Urinary prostaglandin F2alpha is generated from the isoprostane pathway and not the cyclooxygenase in humans. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 2985121

    Urinary prostaglandin F2alpha is generated from the isoprostane pathway and not the cyclooxygenase in humans. Keywords Mesh Terms:

    KEYWORDS: Smoking

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: Urinary prostaglandin F2alpha is generated from the isoprostane pathway and not the cyclooxygenase in humans. Information

    Substance Name: Prostaglandin-Endoperoxide Synthases

    Registry Number: EC 1.14.99.1

    Grant and Affiliation Information for Urinary prostaglandin F2alpha is generated from the isoprostane pathway and not the cyclooxygenase in humans.

    AFFILIATION: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NCRR

    GRANT: RR00095

    ACRONYM: RR

    MEDLINETA: J Biol Chem

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