EFFECTS OF ORGANOMETALS ON CELLULAR SIGNALING .2. INHIBITION OF REINCORPORATION OF FREE ARACHIDONIC-ACID AND INFLUENCE ON PAF-ACETHER SYNTHESIS BY TRIETHYLLEAD
Hf. Krug et al., EFFECTS OF ORGANOMETALS ON CELLULAR SIGNALING .2. INHIBITION OF REINCORPORATION OF FREE ARACHIDONIC-ACID AND INFLUENCE ON PAF-ACETHER SYNTHESIS BY TRIETHYLLEAD, Environmental health perspectives, 102, 1994, pp. 331-334
Organometal compounds affect many enzymes, especially those containing
SH-groups as acyl- and acetyltransferases involved in lysophospholipi
d reacylation. In HL-60 cells, organotin and -lead compounds stimulate
phospholipase A(2) activity, contributing thus to increase the lever
of lysophospholipids In the present study, we have tested whether paf-
acether (paf) biosynthesis was affected by treatment with triethyllead
(Et(3)PbCl) in HL-60 cells. Et(3)PbCl inhibits the incorporation of e
xogenous arachidonic acid in the presence of high (greater than or equ
al to 50 mu M) but not low concentrations (less than or equal to 1 mu
M). High concentrations of the lead compound are unable to induce oaf
formation by itself, however, lower concentrations (less than or equal
to 10 mu M) acted synergistically with TPA or fMLP to stimulate oaf f
ormation. Whereas unstimulated cells produced 0.4 pmole paf/2 x 10(6)
cells, the stimulation with low fMLP (0.1 mu M) resulted in the synthe
sis of 1.7 pmole and with low TPA (2 ng/ml) in 0.5 pmole paf. Preincub
ation of the cells with 10 mu M Et(3)PbCl for 20 to 30 min increased t
he amount of paf formed by these cells to 3.3 pmole after treatment wi
th 0.1 mu M fMLP and 1.5 pmole after TPA. Furthermore, the results sho
wed an inhibition of acetyltransferase (the key enzyme of paf synthesi
s) by the high and not by low concentrations of the lead compound. We
conclude that low concentrations of Et(3)PbCl (less than or equal to 1
0 mu M) may act as a synergistic inducer of paf synthesis initiated vi
a a receptor-coupled stimulation.