Involvement of the lysosome in the catabolism of intracellular lysophosphatidylcholine and evidence for distinct pools of lysophosphatidylcholine.
The role of the lysosome in the metabolism of lysophosphatidylcholine was investigated in isolated rat hepatocytes. Chloroquine, primaquine, and ammonium chloride caused a 2.5-fold increase in radioactive lysophosphatidylcholine in [methyl-3H]choline-labeled cells. This effect was confirmed by a 1.7-fold increase in lysophosphatidylcholine mass in chloroquine-treated hepatocytes. Chloroquine caused a 2.7-fold increase in radioactive lysophosphatidylethanolamine in [1-3H]ethanolamine-labeled cells and a 2.3-fold increase in radioactive lysophosphatidylcholine in [methyl-3H]methionine-labeled cells. Chloroquine did not affect formation of choline-containing aqueous metabolites or the level of radioactivity in phosphatidylcholine (PC). The effect of chloroquine on radioactive lysophosphatidylcholine accumulation was concentration-dependent and occurred within 10 min, consistent with rapid inhibition of lysosomal function. As there was no observed decrease in the 3H in PC, the accumulation of lysophosphatidylcholine was likely due to the inhibition of acid lysophospholipase activity in chloroquine-treated cells. The accumulation of lysophosphatidylcholine in the presence of chloroquine was observed in both short-term- (30 min) and equilibrium-(24 h) [methyl-3H]choline-labeled cells. Simultaneous incubation of hepatocytes with both albumin and chloroquine increased the radioactivity in lysophosphatidylcholine in the medium independently of the accumulation of radioactive lysophosphatidylcholine in the cells. The results suggest that there are separate pools of lysophosphatidylcholine in the hepatocyte and that the pool donated to an extracellular acceptor is different from the lysosomal pool.(ABSTRACT TRUNCATED AT 250 WORDS)
Hatch
G M
GM
Lipid and Lipoprotein Research Group, University of Alberta, Edmonton, Canada.
Oskin
A
A
Vance
D E
DE
D000418:Albumins / Q000494:pharmacology; D000818:Animals; D020126:Brefeldin A; D002738:Chloroquine / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D003517:Cyclopentanes / Q000494:pharmacology; D003566:Cytidine Diphosphate Choline / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism; D008745:Methylation; D010713:Phosphatidylcholines / Q000378:metabolism; D051381:Rats; D014316:Tritium
D000418:Albumins; D003517:Cyclopentanes; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D014316:Tritium; D020126:Brefeldin A; D003566:Cytidine Diphosphate Choline; D002738:Chloroquine; D008715:Methionine; D002794:Choline