title: Identification of novel oxidized levuglandin D2 in marine red alga and mouse tissue.
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).
authors: Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 981-8555, Japan.
authors: Yoshikazu
authors: Y
authors: Kanai
authors: Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 981-8555, Japan.
authors: Sadahiko
authors: S
authors: Hiroki
authors: RIKEN Advanced Science Institute, Wako, Saitama 351-0198, Japan.
authors: Hiroyuki
authors: H
authors: Koshino
authors: Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 981-8555, Japan.
authors: Keiichi
authors: K
authors: Konoki
authors: Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 981-8555, Japan.
authors: Yuko
authors: Y
authors: Cho
authors: National Fisheries Research and Development Institute, Quezon City 1103, The Philippines.
authors: Mirriam
authors: M
authors: Cayme
authors: Asian Natural Environmental Science Center, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
authors: Yasuo
authors: Y
authors: Fukuyo
authors: Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 981-8555, Japan. Electronic address: myama@biochem.tohoku.ac.jp.
authors: Mari
authors: M
authors: Yotsu-Yamashita
mesh_terms: D000818:Animals; D059001:Aquatic Organisms / Q000737:chemistry*; D016718:Arachidonic Acid / Q000494:pharmacology; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002457:Cell Extracts; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D003545:Cysteine / Q000737:chemistry; D044724:Gracilaria / Q000737:chemistry*; D006801:Humans; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D011453:Prostaglandins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D013057:Spectrum Analysis; D013438:Sulfhydryl Compounds / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D002457:Cell Extracts; D011453:Prostaglandins; D013438:Sulfhydryl Compounds; C570744:levuglandin D2; D002084:Butylated Hydroxytoluene; D016718:Arachidonic Acid; C016658:phorbolol myristate acetate; D003545:Cysteine; D013755:Tetradecanoylphorbol Acetate; D015230:Prostaglandin D2