Identification of novel oxidized levuglandin D2 in marine red alga and mouse tissue

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 gamma-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).-Kanai, Y., S. Hiroki, H. Koshino, K. Konoki, Y. Cho, M. Cayme, Y. Fukuyo, and M. Yotsu-Yamashita. Identification of novel oxidized levuglandin D-2 in marine red alga and mouse tissue. J. Lipid Res. 2011. 52: 2245-2254.