+ Translate

Regulation of leukocyte and platelet lipoxygenases by hydroxyeicosanoids

, : Regulation of leukocyte and platelet lipoxygenases by hydroxyeicosanoids. Biochemical Pharmacology 31(21): 3463-3467

During allergic and inflammatory reactions, arachidonic acid is oxidized by lipoxygenases to a variety of biologically active products, including leukotrienes. The mechanisms for regulation of the different lipoxygenase activities are not well defined. We report here that [14C]arachidonic acid metabolism by the 5- and 15-lipoxygenase activities in rabbit leukocytes and the 12-lipoxygenase in rabbit platelets is inhibited by various hydroxyeicosatetraenoic acids (HETEs). 15-HETE was the most effective inhibitor of the 5- and 12-lipoxygenases, whereas similar inhibitory potencies were observed for 5-HETE and 12-HETE acting on the 15-lipoxygenase. These three enzyme pathways were all least sensitive to their own products HETEs. To determine which structural characteristics of 15-HETE are essential for inhibition of the 5-lipoxygenase, various derivatives were prepared and purified by high pressure liquid chromatography, and their structures were confirmed by gas chromatography-mass spectrometry. The inhibitory potencies of 15-HETE analogs with different degrees of unsaturation were in the order of three double bonds greater than 4 greater than 2 greater than 0. 15-Hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE) was four times more potent than 15-HETE. The 15-acetoxy, 15-keto and methyl ester derivatives were of comparable activity to 15-HETE, and the 15-acetoxy methyl ester derivative was less potent. Based upon the observed patterns of inhibition, we postulate that complex interregulatory relationships exist between the various lipoxygenases, and that cells containing these lipoxygenases may interact with each other via their lipoxygenase metabolites.

(PDF 0-2 workdays service)

Accession: 044174719

PMID: 6816247

Submit PDF Full Text: Here

Submit PDF Full Text

No spam - Every submission is manually reviewed

Due to poor quality, we do not accept files from Researchgate

Submitted PDF Full Texts will always be free for everyone
(We only charge for PDFs that we need to acquire)

Select a PDF file:

Related references

Takahashi, Y.; Glasgow, W.C.; Suzuki, H.; Taketani, Y.; Yamamoto, S.; Anton, M.; Kuhn, H.; Brash, A.R., 1993: Investigation of the oxygenation of phospholipids by the porcine leukocyte and human platelet arachidonate 12-lipoxygenases. When arachidonate 12-lipoxygenase purified from porcine leukocytes was incubated aerobically with 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, the phospholipid reacted at up to 30% of the rate of a free fatty acid substrate; the esterif...

Kroneck P.M.H.; Cucurou C.; Ullrich V.; Ueda N.; Suzuki H.; Yoshimoto T.; Matsuda S.; Yamamoto S., 1991: Porcine leukocyte 5 lipoxygenases and 12 lipoxygenases are iron enzymes. 5- and 12-lipoxygenases isolated from porcine leukocytes were investigated by electron paramagnetic resonances at X-band and atomic absorption spectroscopy. For comparison potato 5-lipoxygenase was studied under identical experimental conditions....

Pifer, M.A.; Maerz, T.; Baker, K.C.; Anderson, K., 2014: Matrix metalloproteinase content and activity in low-platelet, low-leukocyte and high-platelet, high-leukocyte platelet rich plasma (PRP) and the biologic response to PRP by human ligament fibroblasts. American Journal of Sports Medicine 42(5): 1211-1218

Moon D.G.; Beaver J.A.; Fenton J.W.II, 1991: Gamma thrombin can induce the formation of platelet leukocyte contacts coincident with platelet enhancement of leukocyte superoxide anion production. FASEB Journal 5(6): A1470

Zotz, R.J.; Mueller, M.; Mahnke, A.; Genth Zotz, S., 2000: Left atrial platelet and leukocyte activation and platelet-leukocyte-aggregates in patients with spontaneous echo contrast. Circulation 102(18 Supplement): II 429, October 31

Dohan Ehrenfest, D.M.; Bielecki, T.; Jimbo, R.; Barbé, G.; Del Corso, M.; Inchingolo, F.; Sammartino, G., 2013: Do the fibrin architecture and leukocyte content influence the growth factor release of platelet concentrates? An evidence-based answer comparing a pure platelet-rich plasma (P-PRP) gel and a leukocyte- and platelet-rich fibrin (L-PRF). Platelet concentrates for surgical use are tools of regenerative medicine designed for the local release of platelet growth factors into a surgical or wounded site, in order to stimulate tissue healing or regeneration. Leukocyte content and fibrin...

Evangelista, V.; Manarini, S.; Dell'Elba, G.; Martelli, N.; Napoleone, E.; D.S.nto, A.; Lorenzet, P.Savi.Roberto., 2005: Clopidogrel inhibits platelet-leukocyte adhesion and platelet-dependent leukocyte activation. Clopidogrel is considered to be an important therapeutic advance in anti-platelet therapy. We investigated whether inhibition by clopidogrel results in a reduced capacity of platelets to adhere and stimulate pro-atherothrombotic and inflammatory f...

Kroneck, P.M.; Cucurou, C.; Ullrich, V.; Ueda, N.; Suzuki, H.; Yoshimoto, T.; Matsuda, S.; Yamamoto, S., 1991: Porcine leukocyte 5- and 12-lipoxygenases are iron enzymes. 5- and 12-lipoxygenases isolated from porcine leukocytes were investigated by electron paramagnetic resonance at X-band and atomic absorption spectroscopy. For comparison potato 5-lipoxygenase was studied under identical experimental conditions. A...

Katoh, A.; Ikeda, H.; Ueno, T.; Haramaki, N.; Takajo, Y., 1998: Platelet-derived 12-hydroxyeicosatraenoic acid regulates platelet surface expression of adhesion molecules, platelet aggregation and platelet-leukocyte interaction. Circulation 98(17 SUPPL ): I523, Oct 27

Kazemi, D.; Fakhrjou, A., 2015: Leukocyte and Platelet Rich Plasma (L-PRP) Versus Leukocyte and Platelet Rich Fibrin (L-PRF) For Articular Cartilage Repair of the Knee: A Comparative Evaluation in an Animal Model. Articular cartilage injuries of the knee are among the most debilitating injuries leading to osteoarthritis due to limited regenerative capability of cartilaginous tissue. The use of platelet concentrates containing necessary growth factors for ca...