Investigations of human platelet-type 12-lipoxygenase: role of lipoxygenase products in platelet activation
| Autor: | Jesús Ceja, Kenneth Ikei, Theodore R. Holman, Michael Holinstat, Joanne Vesci, Patrick L. Apopa, Jennifer Yeung |
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| Rok vydání: | 2012 |
| Předmět: |
chemistry.chemical_classification
biology Linoleic acid Fatty acid Cell Biology Clot retraction Biochemistry Eicosapentaenoic acid Lipoxygenase chemistry.chemical_compound Endocrinology chemistry biology.protein lipids (amino acids peptides and proteins) Arachidonic acid Platelet activation Beta oxidation |
| Zdroj: | Journal of Lipid Research. 53:2546-2559 |
| ISSN: | 0022-2275 |
| Popis: | Human platelet-type 12-lipoxygenase (12-LOX) has recently been shown to play an important role in regulation of human platelet function by reacting with arachidonic acid (AA). However, a number of other fatty acids are present on the platelet surface that, when cleaved from the phospholipid, can be oxidized by 12-LOX. We sought to characterize the substrate specificity of 12-LOX against six essential fatty acids: AA, dihomo-γ-linolenic acid (DGLA), eicosapentaenoic acid (EPA), α-linolenic acid (ALA), eicosadienoic acid (EDA), and linoleic acid (LA). Three fatty acids were comparable substrates (AA, DGLA, and EPA), one was 5-fold slower (ALA), and two showed no reactivity with 12-LOX (EDA and LA). The bioactive lipid products resulting from 12-LOX oxidation of DGLA, 12-(S)-hydroperoxy-8Z,10E,14Z-eicosatrienoic acid [12(S)-HPETrE], and its reduced product, 12(S)-HETrE, resulted in significant attenuation of agonist-mediated platelet aggregation, granule secretion, αIIbβ3 activation, Rap1 activation, and clot retraction. Treatment with DGLA similarly inhibited PAR1-mediated platelet activation as well as platelet clot retraction. These observations are in surprising contrast to our recent work showing 12(S)-HETE is a prothrombotic bioactive lipid and support our hypothesis that the overall effect of 12-LOX oxidation of fatty acids in the platelet is dependent on the fatty acid substrates available at the platelet membrane. |
| Databáze: | OpenAIRE |
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