ISSN:
0268-2605
Schlagwort(e):
Organolead
;
organomercury
;
organotin
;
toxicity
;
lipid metabolism
;
arachidonic acid
;
Lands cycle
;
cell culture
;
HL-60 cells
;
Chemistry
;
Organic Chemistry
Quelle:
Wiley InterScience Backfile Collection 1832-2000
Thema:
Chemie und Pharmazie
Notizen:
The concentration of free fatty acids within cells is mainly dependent upon the following enzyme activities: liberation by phospholipase A2 (PLA2), activation of free acids by acyl-CoA-synthetase and re-esterification by lysophospholipid acyltransferase (LAT). In many cell types, especially those of the haematopeotic system, this deacylation-reacylation cycle (‘Lands cycle’) plays an important role in the regulation of free fatty acid concentration, above all that of arachidonic acid.We have shown here that heavy-metal compounds affect this cycle mainly at two points and thereby lead to an increase of free fatty acids. On the one hand, organometals cause an inhibition of the reacylation of lysophospholipids; and on the other, the induction of PLA2 activity produces the same result. All compounds investigated such as methylmercury chloride (MeHgCl), diethyltriethyl-, and trimethyl-lead chloride (Et2PbCl2, Et3PbCl, Me3PbCl) as well as trimethyltin chloride (Et3SnCl) and di-t-butyltin dichloride (t-Bu2SnCl2) show at least one of these effects. In the case of Et3PbCl, the use of PLA2-inhibitors or pertussis toxin causes a drastic decrease in the amount of arachidonic acid liberated. These experiments demonstrate that the organometallic compounds inhibit the reacylation and/or stimulate the deacylation of fatty acids that are involved in many important biological or pathological mechanisms. The results suggest that in differentiated HL-60 cells the organometal compounds stimulate the Lands cycle by increasing the activity of the PLA2, possibly via a signal-transduction mechanism, and this effect is intensified via an inhibition of reesterification.
Zusätzliches Material:
7 Ill.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1002/aoc.590060309
Permalink
