Abstract
In animals, the product of cyclooxygenase reacting with arachidonic acid, prostaglandin(PG)H(2), can undergo spontaneous rearrangement and nonenzymatic ring cleavage to form levuglandin(LG)E(2) and LGD(2). 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 LGD(2) (ox-LGD(2)) from the red alga Gracilaria edulis and determined its planar structure. Additionally, ox-LGD(2) 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-LGD(2) is a common oxidized metabolite of LGD(2). In the planar structure of ox-LGD(2), H8 and H12 of LGD(2) 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-LGD(2) is less reactive with amines than LGs. Therefore, ox-LGD(2) might be considered a detoxification metabolite of LGD(2).
Highlights
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
We identified oxidized LGD2 (ox-LGD2) in some tissues of mice using LC-MS/MS and in a phorbol12-myristate-13-acetate (PMA)-stimulated THP-1 cell lysate incubated with arachidonic acid
Ox-LGD2 was identified in mouse tissues and the lysate of PMA-treated THP-1 cells incubated with arachidonic acid
Summary
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 ␥-ketoaldehydes that form covalent adducts with proteins, DNA, and phosphatidylethanolamine in cells. The product of cyclooxygenase (COX) reacting with arachidonic acid, prostaglandin(PG)H2, can undergo spontaneous rearrangement and nonenzymatic ring cleavage to form highly reactive levuglandin (LG)E2 or LGD2 [1], if PGH2 is not utilized by cellular PG synthases. LG, isoLG, and isoprostane esters have not yet been identified in red algae
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