The effect of 3-methylindole on the rates of phospholipid and neutral lipid synthesis in cultured fibroblasts.
The present study was designed to test the hypothesis that a pneumotoxin, 3-methylindole, alters the basic metabolic pathways involved in phospholipid and neutral lipid synthesis in cultured fibroblasts. Rat skin fibroblasts were obtained from day-old pups. Confluent monolayers were preincubated for up to 24 h with a range of concentrations (0-0.76 mM) of 3-methylindole. Following these treatments, the cell lipids were labelled by incubation for 6 h with [14C]glycerol. The lipids were extracted, separated by thin layer chromatography, and the radioactivity in each fraction was determined. 3-Methylindole had no effect on the total incorporation of [14C]glycerol into lipids, but significantly altered the distribution among lipid fractions. Incubation with 3-methylindole caused a decrease in the incorporation of [14C]glycerol into phosphatidylcholine, while radioactivity accumulated in the neutral lipid fraction. The other lipid fractions responded variably. Similarily, Flow 2000 human diploid lung fibroblasts were incubated for 24 h with 3-methylindole followed by treatment with [14C]glycerol, resulting in a 74% decrease in the incorporation of [14C]glycerol into phosphatidylcholine and a 50% increase in its accumulation in neutral lipid. The results indicate that 3-methylindole inhibits the synthesis of phosphatidylcholine from diacylglycerol precursors on the endoplasmic reticulum in cultured fibroblasts. This is an important observation as it shows that 3-methylindole affects the synthesis of phospholipids required for membrane turnover in cells that are not specialized for the production of phospholipids for surfactant.
Kirkland
J B
JB
Department of Nutritional Sciences, College of Biological Science, University of Guelph, Ont., Canada.
Bray
T M
TM
Bettger
W J
WJ
D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007700:Kinetics; D008055:Lipids / Q000096:biosynthesis*; D008168:Lung / Q000378:metabolism; D010743:Phospholipids / Q000096:biosynthesis*; D051381:Rats; D012862:Skatole / Q000494:pharmacology*; D012867:Skin / Q000378:metabolism
D007211:Indoles; D008055:Lipids; D010743:Phospholipids; D012862:Skatole; D005990:Glycerol