Journal of Lipid Research
Volume 52, Issue 12, December 2011, Pages 2245-2254
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Research Articles
Identification of novel oxidized levuglandin D2 in marine red alga and mouse tissue

https://doi.org/10.1194/jlr.M017053Get rights and content
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In animals, the product of cyclooxygenase reacting with arachidonic acid, prostaglandin(PG)H2, can undergo spontaneous rearrangement and nonenzymatic ring cleavage to form levuglandin(LG)E2 and LGD2. These LGs and their isomers are highly reactive γ-ketoaldehydes that form covalent adducts with proteins, DNA, and phosphatidylethanolamine in cells. Here, we isolated a novel oxidized LGD2 (ox-LGD2) from the red alga Gracilaria edulis and determined its planar structure. Additionally, ox-LGD2 was identified in some tissues of mice and in the lysate of phorbol-12-myristate-13-acetate (PMA)-treated THP-1 cells incubated with arachidonic acid using LC-MS/MS. These results suggest that ox-LGD2 is a common oxidized metabolite of LGD2. In the planar structure of ox-LGD2, H8 and H12 of LGD2 were dehydrogenated and the C9 aldehyde was oxidized to a carboxylic acid, which formed a lactone ring with the hydrated ketone at C11. These structural differences imply that ox-LGD2 is less reactive with amines than LGs. Therefore, ox-LGD2 might be considered a detoxification metabolite of LGD2.

prostaglandins
Gracilaria
LC-MS/MS
NMR

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This work was supported by the Cabinet Office of the Government of Japan through its funding program for the Next-Generation World-Leading Researchers (LS012) and by the Japan Society for the Promotion of Science through Grant-in-Aid for Scientific Research No. 21380070.

    Abbreviations:

    COSY

    correlation spectroscopy

    HMBC

    heteronuclear multiple-bond correlation

    HSQC

    heteronuclear single-quantum coherence

    LG

    levuglandin

    isoLG

    isolevuglandin

    ox-LGD2

    oxidized levuglandin D2

    MRM

    multiple reaction monitoring

    PG

    prostaglandin

    PMA

    phorbol-12-myristate-13-acetate

    ROESY

    rotating-frame Overhauser enhancement spectroscopy

    TOCSY

    total correlation spectroscopy

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of eight figures.