Activation of caspase 3 in HepG2 cells by elaidic acid (t18:1).
In order to examine the effects of trans-unsaturated fatty acids (TFAs) on HepG2 cells, cells were grown in serum-free media supplemented with elaidic acid (t18:1); t18:1 is the trans-isomer of oleic acid and is the major component of TFAs in foods. Both t18:1 and palmitic acids (16:0) at concentrations higher than 100 microM inhibited growth and decreased the rate of protein synthesis. The presence of phosphatidylserine in the outer leaflet of the lipid bilayer, indicative of apoptosis, occurred 1 h after the addition of both t18:1 and 16:0 to the media. Caspase 3 was found to be activated by these fatty acids: caspase 8 was activated by 16:0 and only moderately by t18:1. Activation of caspase 3 by these fatty acids was fully inhibited by a caspase 8 inhibitor. However, growth inhibition by t18:1 was partially prevented by the caspase 8 inhibitor. These results suggest that cell death caused by t18:1 may proceed by both caspase-dependent and -independent pathways.
Kondoh
Yumi
Y
Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto, Japan.
Kawada
Teruo
T
Urade
Reiko
R
D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism; D061945:Caspase Inhibitors; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020717:Eukaryotic Initiation Factor-2B / Q000378:metabolism; D006801:Humans; D019301:Oleic Acid / Q000494:pharmacology*; D009829:Oleic Acids; D019308:Palmitic Acid / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D020717:Eukaryotic Initiation Factor-2B; D009829:Oleic Acids; D010768:Phosphoserine; D019301:Oleic Acid; D019308:Palmitic Acid; C011459:elaidic acid; D053148:Caspase 3; D053453:Caspase 9