The stimulation of arachidonic acid metabolism by organic lead and tin compounds in human HL-60 leukemia cells

Kafer, Andrea; Zöltzer, H; Krug, Harald F.

doi:10.1016/0041-008x(92)90153-j

Cited by 15 publications

(6 citation statements)

References 28 publications

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“…Kafer et al [59] showed that stimulation of HL-60 human leukemia cells by organic lead and tin compounds induced an increase in arachidonic acid release, wherein redistribution occurs within tissue lipid classes. The increase of free arachidonic acid for prostanoid formation was observed prior to cell death in culture.…”

Section: Heavy Metals and Pufamentioning

confidence: 98%

Dietary PUFA and flavonoids as deterrents for environmental pollutants

Watkins

Hannon

Ferruzzi

et al. 2007

The Journal of Nutritional Biochemistry

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Section: Heavy Metals and Pufamentioning

confidence: 98%

Dietary PUFA and flavonoids as deterrents for environmental pollutants

Watkins

Hannon

Ferruzzi

et al. 2007

The Journal of Nutritional Biochemistry

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“…In this study it is well documented that in leukocytes of lead-exposed workers the amount of arachidonic acid is significantly increased and the production of LTB4 after stimulation with fMLP is significantly higher than in the control group. We described earlier comparable effects on the arachidonic acid metabolism for other organometals as well (8,18) and the assumption could be made that these compounds may lead in vivo to increase in the level of lipid mediators, eicosanoids and paf, which are considered as potent mediators of inflammatory, allergic, and pseudoallergic reactions (21,23).…”

Section: Discussionmentioning

confidence: 99%

“…This may lead to the assumption that the stimulated activity of the PLA2 rises the amount of lyso paf as well as of arachidonic acid when cells were treated with the organometal compounds. We tested therefore the effect of Et3PbCl, a severely toxic organometal compound (8), on the activity of acetyltransferase. This enzyme is located at the same cellular site as the acyltransferase within the HL-60 cells (13).…”

Section: Discussionmentioning

confidence: 99%

“…More and more investigations have shown that environmental toxicants as heavy metal compounds affect this sensitive mechanism within human blood platelets (1)(2)(3)(4), macrophages (5), granulocytes (6)(7)(8), as well as in fibroblasts (9). These xenobiotics enhance the deacylation either via the activation of phospholipase A2 (2,7,8) or the inhibition of fatty acid-CoA synthetase or lysophospholipid acyltransferase (4)(5)(6) lipid mediators. Another important pathway coupled to this deacylation-reacylation cycle is involved in paf production, a very potent mediator of anaphylaxis and inflammation (10): The acetylation of lyso paf-acether (lyso paf, 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine) by the activity of the key enzyme lyso paf:acetyl-CoA acetyltransferase mediates the biosynthesis of paf (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

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Effects of organometals on cellular signaling. II. Inhibition of reincorporation of free arachidonic acid and influence on paf-acether synthesis by triethyllead.

Krug

Mattern

Bidault

et al. 1994

Environ Health Perspect

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Organometal compounds affect many enzymes, especially those containing SH-groups as acyl-and acetyltransferases involved in lysophospholipid reacylation. In HL-60 cells, organotin and -lead compounds stimulate phospholipase A2 activity, contributing thus to increase the level of lysophospholipids. In the present study, we have tested whether paf-acether (paf) biosynthesis was affected by treatment with triethyllead (Et3PbCI) in HL-60 cells. Et3PbCI inhibits the incorporation of exogenous arachidonic acid in the presence of high (1 50 pM) but not low concentrations (< 1 pM). High concentrations of the lead compound are unable to induce paf formation by itself, however, lower concentrations (< 10 pM) acted synergistically with TPA or fMLP to stimulate paf formation. Whereas unstimulated cells produced 0.4 pmole paf/2 x 106 cells, the stimulation with low fMLP (0.1 pM) resulted in the synthesis of 1.7 pmole and with low TPA (2 ng/ml) in 0.5 pmole paf. Preincubation of the cells with 10 pM Et3PbCI for 20 to 30 min increased the amount of paf formed by these cells to 3.3 pmole after treatment with 0.1 pM fMLP and 1.5 pmole after TPA. Furthermore, the results showed an inhibition of acetyltransferase (the key enzyme of paf synthesis) by the high and not by low concentrations of the lead compound. We conclude that low concentrations of Et3PbCI (< 10 pM) may act as a synergistic inducer of paf synthesis initiated via a receptor-coupled stimulation. -Environ Health Perspect 102(Suppl 3): 331-334 (1994).

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“…Upon stimulation with A 23187, fMLP, and various organometals, HL-60 cells showed increased levels of free arachidonic acid (18)(19)(20). The effect of different substances on the organometal-induced AA liberation was examined.…”

Section: Resuftsmentioning

confidence: 99%

Effects of organometals on cellular signaling. I. Influence of metabolic inhibitors on metal-induced arachidonic acid liberation.

Kafer

Krug

1994

Environ Health Perspect

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Organic lead and tin compounds stimulate an increase of free arachidonic acid (AA) in HL-60 cells. This fatty acid is involved in numerous health problems and physiological mechanisms. Three major pathways result in a liberation of AA from membrane phospholipids and there is evidence that G-proteins serve as couplers within all three pathways. Therefore we investigated the influence of pertussis toxin (PT) on the organometallic-induced AA liberation. The effect of all studied compounds (organotin and organo-lead) was diminished by PT. We conclude that the organometals activate PLA2 to some extent via a PT-sensitive pathway. The ionophor A 23187 (1-10 microM) led to an increase of free AA by raising the intracellular Ca2+ level. One of the postulated ways of AA release is via Ca2+ channel activation; phospholipases are Ca2+ dependent. Thus, we examined the necessity of free intracellular Ca2+ for the organometallic effect. The Ca2+ chelator EGTA inhibited the increase of free AA induced by organometals. This is true also for verapamil, a Ca2+ channel blocker. Quinacrine, which is thought to be an inhibitor of phospholipase A2 (PLA2), prevented the AA liberation from membrane phospholipids induced by organometals. This could be due to the inhibition of PLA2, but it could also be the result of an inhibited Ca2+ influx.

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The stimulation of arachidonic acid metabolism by organic lead and tin compounds in human HL-60 leukemia cells

Cited by 15 publications

References 28 publications

Dietary PUFA and flavonoids as deterrents for environmental pollutants

Dietary PUFA and flavonoids as deterrents for environmental pollutants

Effects of organometals on cellular signaling. II. Inhibition of reincorporation of free arachidonic acid and influence on paf-acether synthesis by triethyllead.

Effects of organometals on cellular signaling. I. Influence of metabolic inhibitors on metal-induced arachidonic acid liberation.

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