1-ACYL-2 ACETYL-SN-GLYCERO-3 PHOSPHOCHOLINE DECREASES THE SUSCEPTIBILITY OF LOW-DENSITY-LIPOPROTEIN TO OXIDATIVE MODIFICATION BY COPPER IONS, MONOCYTES OR ENDOTHELIAL-CELLS
C. Maziere et al., 1-ACYL-2 ACETYL-SN-GLYCERO-3 PHOSPHOCHOLINE DECREASES THE SUSCEPTIBILITY OF LOW-DENSITY-LIPOPROTEIN TO OXIDATIVE MODIFICATION BY COPPER IONS, MONOCYTES OR ENDOTHELIAL-CELLS, Biochimica et biophysica acta, L. Lipids and lipid metabolism, 1210(2), 1994, pp. 233-238
The effects of platelet-activating factor (PAF) and its analogue, 1 ac
yl-2 acetyl-sn-glycero-3 phosphocholine (1 acyl-2 acetyl-GPC), were in
vestigated on the oxidative modification of low-density lipoprotein (L
DL) by copper ions, U937 monocyte-like cells or endothelial cells, by
determination of the lipid peroxidation end products (TBARS) content a
nd measurement of the electrophoretic mobility of the particle. 1 Acyl
-2 acetyl-GPC, in the concentration range 1-5 mu g/ml, inhibited LDL o
xidation in a dose-dependent manner in the three systems, whereas PAF
had no effect. The protective effect of 1 acyl-2 acetyl-GPC was marked
ly more important when oxidative modification was performed with endot
helial cells, leading to total inhibition at 5 mu g/ml. At the same co
ncentration, the TBARS production was inhibited by 60% and 20% with mo
nocytes and copper ions, respectively. The degradation by J774 macroph
age-like cells of LDL modified by copper ions, U937 monocyte-like cell
s or endothelial cells was also inhibited when modification was perfor
med in the presence of 1 acyl-2 acetyl-GPC. Furthermore, preincubation
of the LDL particle with 1 acyl-2 acetyl-GPC before modification prot
ected the lipoprotein against oxidation, whereas preincubation of the
cultured cells with the phospholipid had no effect. Thus 1 acyl-2 acet
yl-GPC decreases the susceptibility of the LDL particle to oxidative m
odification, possibly by intercalation within the lipid phase of the p
article. Since LDL oxidation is believed to play an important role in
the initiation and progression of atherosclerosis, this inhibitory eff
ect of 1 acyl-2 acetyl-GPC might be of importance in view of the fact
that this phospholipid is produced concomitantly with PAF in some infl
ammatory cells.