RRC ID 18625
Author Kanai Y, Hiroki S, Koshino H, Konoki K, Cho Y, Cayme M, Fukuyo Y, Yotsu-Yamashita M.
Title Identification of novel oxidized levuglandin D2 in marine red alga and mouse tissue.
Journal J Lipid Res
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).
Volume 52(12)
Pages 2245-2254
Published 2011-12-1
DOI 10.1194/jlr.M017053
PII S0022-2275(20)40828-4
PMID 21893678
PMC PMC3220291
MeSH Animals Aquatic Organisms / chemistry* Arachidonic Acid / pharmacology Butylated Hydroxytoluene / pharmacology Cell Extracts Cell Line, Tumor Chromatography, Liquid Cysteine / chemistry Gracilaria / chemistry* Humans Male Mice Oxidation-Reduction Prostaglandin D2 / analogs & derivatives* Prostaglandin D2 / analysis Prostaglandin D2 / chemistry Prostaglandin D2 / metabolism Prostaglandins / analysis* Prostaglandins / chemistry Prostaglandins / metabolism Spectrum Analysis Sulfhydryl Compounds / metabolism Tandem Mass Spectrometry Tetradecanoylphorbol Acetate / analogs & derivatives Tetradecanoylphorbol Acetate / pharmacology
IF 4.483
Times Cited 5
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Human and Animal Cells THP-1(RCB1189)