Metabolism of cyclooxygenase and lipoxygenase products by 15-prostaglandin dehydrogenase from human HL-60 leukemia cells

Agins, A. P.; Zipkin, Robert E.; Taffer, Ira M.

doi:10.1007/bf01966527

Cited by 9 publications

(8 citation statements)

References 5 publications

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“…We have also demonstrated that differentiated HL-60 cells have about 2-3 times more lysophospholipase activity than do undifferentiated cells. The results shown in Table 1 are similar to results obtained by previous investigators [3][4][5][6][7][8]. The increased phospolipase A2 activity could potentially cause an increase in the levels of lysophospholipids which, if high enough, could be cytotoxic.…”

Section: Discussionsupporting

confidence: 89%

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Butyric acid-induced differentiation of HL-60 cells increases the expression of a single lysophospholipase

Garsetti¹,

Holtsberg²,

Steiner

et al. 1992

Biochemical Journal

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Treatment of HL-60 cells with 0.5 mM-butyric acid resulted in morphological changes, including the formation of cytoplasmic granules, nuclear condensation and segmentation. These differentiated cells had an elevated phospholipase A2 activity and an increased capacity to synthesize a variety of eicosanoids, including both lipoxygenase and cyclooxygenase products. Phospholipase A2-mediated release of arachidonic acid is accompanied by an equimolar production of potentially cytotoxic lysophospholipid. In association with the differentiation process, there was a 2-3-fold increase in lysophospholipase activity. Subsequent studies were undertaken to identify and characterize the lysophospholipases in this cell system, with 1-[1-14C]palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine as substrate. Hydrophobic chromatography of both undifferentiated and differentiated cell extracts revealed three peaks of enzyme activity. Extracts of differentiated cells contained a dramatic increase in activity contained in peak 2. The increase in enzymic activity of peak 2 appeared to account for the increase in total lysophospholipase activity found in the differentiated cell homogenates. The lysophospholipases contained in peaks 2 and 3 were purified to homogeneity and were 20 and 22 kDa respectively, as determined by denaturing polyacrylamide-gel electrophoresis. Peaks 2 and 3 were similar on the basis of amino acid composition, but had distinctive C-terminal peptide amino acid sequences. Enzymic characterization of these proteins demonstrated that there was no detectable level of non-specific esterase, acyltransferase or transacylase activity associated with these proteins. We concluded that peak 2 lysophospholipase is regulated by differentiation in HL-60 cells and may play an important role in protecting these cells from the cytolytic effects of the lysophospholipids produced by the activation of phospholipase A2.

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Section: Discussionsupporting

confidence: 89%

“…Differentiated HL-60 cells have increased capacity for the production ofa number ofproinflammatory mediators, including eicosanoids [4][5][6]. Phospholipase A2 activity has also been shown to increase upon differentiation of the HL-60 cells [7].…”

Section: Introductionmentioning

confidence: 99%

Butyric acid-induced differentiation of HL-60 cells increases the expression of a single lysophospholipase

Garsetti¹,

Holtsberg²,

Steiner

et al. 1992

Biochemical Journal

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“…Evidence was obtained that 15-hydroxyprostaglandin dehydrogenase (NAD+) (15-PGDH; EC 1.1.1.141) activity was downregulated in AML, due to the massively reduced plasma levels of 15-keto-PGE2, which was detected in only 1/20 AML plasma samples. HL-60 cells have been reported to possess this metabolic activity with respect to PGE2 and 15-HETE [44]. Both of these activities in vivo were observed in this study to be diminished in AML patients.…”

Section: Discussionsupporting

confidence: 67%

The plasma lipidome in acute myeloid leukemia at diagnosis in relation to clinical disease features

et al. 2017

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BackgroundEarly studies established that certain lipids were lower in acute myeloid leukemia (AML) cells than normal leukocytes. Because lipids are now known to play an important role in cell signaling and regulation of homeostasis, and are often perturbed in malignancies, we undertook a comprehensive lipidomic survey of plasma from AML patients at time of diagnosis and also healthy blood donors.MethodsPlasma lipid profiles were measured using three mass spectrometry platforms in 20 AML patients and 20 healthy blood donors. Data were collected on total cholesterol and fatty acids, fatty acid amides, glycerolipids, phospholipids, sphingolipids, cholesterol esters, coenzyme Q10 and eicosanoids.ResultsWe observed a depletion of plasma total fatty acids and cholesterol, but an increase in certain free fatty acids with the observed decline in sphingolipids, phosphocholines, triglycerides and cholesterol esters probably driven by enhanced fatty acid oxidation in AML cells. Arachidonic acid and precursors were elevated in AML, particularly in patients with high bone marrow (BM) or peripheral blasts and unfavorable prognostic risk. PGF2α was also elevated, in patients with low BM or peripheral blasts and with a favorable prognostic risk. A broad panoply of lipid classes is altered in AML plasma, pointing to disturbances of several lipid metabolic interconversions, in particular in relation to blast cell counts and prognostic risk.ConclusionsThese data indicate potential roles played by lipids in AML heterogeneity and disease outcome.General significanceEnhanced catabolism of several lipid classes increases prognostic risk while plasma PGF2α may be a marker for reduced prognostic risk in AML.

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“…The latter would be the first reaction products, and, in the case of C18 PUFAs, would be also subject to oxidation to keto acids, a process which is not likely to occur non-enzymically because it cannot be observed with C20 PUFAs or DHA. No interconversion between 9-hydroxy and 9-keto acids was found in contrast to the situation described in mammalian tissues (Agins et al, 1987;Earles et al, 1991).…”

Section: Discussioncontrasting

confidence: 81%

Polyunsaturated-fatty-acid oxidation in Hydra: regioselectivity, substrate-dependent enantioselectivity and possible biological role

Marzo

Gianfrani

Petrocellis

et al. 1994

Biochemical Journal

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A novel and abundant lipoxygenase-like activity converting cis-eicosa-5,8,11,14-tetraenoic acid (arachidonic acid) into (11R)-hydroxyeicosatetraenoic acid has been recently described in homogenates of the freshwater hydrozoan Hydra vulgaris. In this study, other substrates for this enzyme were selected from the polyunsaturated fatty acids (PUFAs) present in H. vulgaris, and the chemical natures of the hydroperoxy and hydroxy derivatives produced, as well as the activity of some of the latter on hydroid tentacle regeneration, were investigated. The highest conversion among C20 fatty acids was observed for arachidonic acid, and among C18 fatty acids for cis-octadeca-9,12,15- and cis-octadeca-6,9,12-trienoic (alpha- and gamma-linolenic) acids. Cis double bonds on the 10th carbon atom from the aliphatic end of the substrate (e.g. C-9, C-11 and C-13 respectively in C18, C20 and C22 PUFAs) were regiospecifically peroxidized. Conversely, trans-octadeca-9,12-dienoic (linoelaidic) acid was not a substrate for lipoxygenase activity. Enantioselectivity of lipoxygenation depended on the degree of unsaturation of the substrate, with the amount of the R enantiomer increasing when passing, for example, from cis-eicosa-11,14-dienoic to cis-eicosa-5,8,11,14,17-pentaenoic acid. Regiospecific formation of keto acids was observed only when incubating C18 PUFAs. Commercially available hydroxyacids corresponding to the reaction products of some of the most abundant H. vulgaris PUFAs were tested for effects on Hydra tentacle regeneration. An enhancement of average tentacle number, in a fashion depending on the stereochemistry and on the number of double bonds, was found for two compounds, thus suggesting for the 11-lipoxygenase-like enzyme a role in the production of metabolites potentially active in the control of hydroid regenerative processes.

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Metabolism of cyclooxygenase and lipoxygenase products by 15-prostaglandin dehydrogenase from human HL-60 leukemia cells

Cited by 9 publications

References 5 publications

Butyric acid-induced differentiation of HL-60 cells increases the expression of a single lysophospholipase

Butyric acid-induced differentiation of HL-60 cells increases the expression of a single lysophospholipase

The plasma lipidome in acute myeloid leukemia at diagnosis in relation to clinical disease features

Polyunsaturated-fatty-acid oxidation in Hydra: regioselectivity, substrate-dependent enantioselectivity and possible biological role

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