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

Abstract

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).

Anti-Inflammatory Activity of Oleanolic Acid by Inhibition of Secretory Phospholipase A2

“…Cyclooxygenase-1/2 (COX-1/2) and lipoxygenase (LOX) catalyze arachidonic acid into proinflammatory mediators such as prosta-glandins, thromboxanes, and leukotrienes, respectively. A lysophospholipid pool containing traces of alkyl lysophospholipids is further converted into platelet activation factor (PAF) by acetyltransferase [6]. Present anti-inflammatory therapies include the non-steroidal anti-inflammatory drugs that inhibit either LOX or COX-1/2 enzymes.…”