Resistance of HepG2 cells against the adverse effects of ethanol related to neutral lipid and phospholipid metabolism.
The influence of both short- and long-term ethanol exposure on the lipid metabolism was determined in the human hepatoma cell line HepG2. Ethanol did not cause any cytotoxicity or lipid peroxidation even after 7 days of 100 mM ethanol treatment of HepG2 cells. Incubation of cells in the presence of [1-(14)C]ethanol demonstrated that these cells actively metabolize ethanol to acetyl CoA, incorporating the radioactive label into neutral lipids and phospholipids. [1,2,3-(3)H]glycerol was efficiently used in phospholipid and neutral lipid biosynthesis, showing higher radioactivity in phosphatidylcholine, phosphatidylethanolamine and triacylglycerols. Exposure of HepG2 cells to 100 mM ethanol for 24 hr did not significantly modify the incorporation of glycerol into newly synthesized phospholipids and neutral lipids, nor was lipid degradation affected by the presence of ethanol. When the alcohol treatment was prolonged for 7 days, incorporation of [1,2,3-(3)H]glycerol into triacylglycerols and diacylglycerols showed a slight increase concomitantly with decreased radioactivity in the major phospholipids, phosphatidylcholine and phosphatidylethanolamine. In addition, these changes were associated with a greater release of radiolabeled triacylglycerols into the culture medium. These results indicate that ethanol does not cause in HepG2 cells the marked lipogenic stimulation widely shown in hepatocytes, and demonstrate that HepG2 cells strongly resist the adverse effects of ethanol. Since these cells lack the isoenzymatic form of cytochrome P(450) mainly involved in the ethanol metabolism (namely cytochrome P(450)2E1) and also are devoid of alcohol dehydrogenase activity, we propose that the toxic actions of ethanol on liver must be linked to the activity of one or both of these systems.
Jiménez-López
José M
JM
Faculty of Sciences, Department of Biochemistry and Molecular Biology, University of Granada, Avenida Fuentenueva s/n, Granada 18001, Spain.
Carrasco
María P
MP
Segovia
Josefa L
JL
Marco
Carmen
C
D000704:Analysis of Variance; D000431:Ethanol / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D010743:Phospholipids / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D010743:Phospholipids; D000431:Ethanol