Conversion of 5,6‐dihydroxyeicosatetraenoic acids A novel pathway for lipoxin formation by human platelets

FEBS Letters

Lindgren, Jan Åke¹  Edenius, Charlotte¹  Lellouche, Jean-Paul²  Tornhamre, Susanne¹  Gigou, Agnès² 

[1] Department of Physiological Chemistry, Karolinska Institutet, S-104 01 Stockholm, Sweden;CEN Saclay-Service de Molécules Marquées, 91191 Gif-Sur-Yvette, France

关键词: Lipoxin;    5;    6-Dihydroxyeicosatetraenoic acid;    12-Lipoxygenase;    Human platelet;   

DOI  :  10.1016/0014-5793(92)80593-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Leukotriene A₄ may be metabolized to 5(S),6(R)- and 5(S),6(S)-dihydroxy-7,9-trans-11,14-cis-eicosatetraenoic acids by enzymatic or non-enzymatic hydrolysis. Incubation of human platelet suspensions with these dihydroxy acids led to the formation of lipoxin A₄ and 6(S)-lipoxin A₄ via lipoxygenation at C-15. Furthermore, human platelets converted the two 5(R),6(S)- and 5(R),6(R)-dihydroxy-7,9-trans-11,14-cis-eicosatetraenoic acids to tetraene-containing trihydroxyeicosatetraenoic acids. In contrast, leukotrienes C₄, D₄ and E₄ were not transformed to cysteinyl-lipoxins, Time-course studies of leukotriene A₄ metabolism in human platelet suspensions indicated lipoxin formation via two pathways: (i) direct conversion of leukotriene A₄, leading to formation of the lipoxin intermediate 15-hydroxy-leukotriene A₄; and (ii) 15-lipoxygenation of the 5(S),6(R)- and 5(S),6(S)-dihydroxyeicosatetraenoic acids. The results demonstrate that lipoxygenation at C-15 of 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acids may be an alternative novel pathway for platelet-dependent lipoxin formation.

【 授权许可】

Unknown