Fatty acid ethyl esters decrease human hepatoblastoma cell proliferation and protein synthesis

Zbigniew M. Szczepiorkowski, G. Richard Dickersin, Michael Laposata

Research output: Contribution to journalArticle

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Abstract

Background/Aims: Fatty acid ethyl esters (FAEEs) are nonoxidative products of ethanol metabolism. They have been implicated as mediators of ethanol-induced organ damage because FAEE and FAEE synthase have been found specifically in the organs damaged by ethanol abuse. This study showed toxicity specifically related to FAEE or their metabolites for intact human hepatoblastoma-derived cells (HepG2). Methods: The lipid core of human low-density lipoprotein (LDL) was extracted and the LDL particle reconstituted with either ethyl oleate or ethyl arachidonate. Cultured HepG2 cells were incubated with LDL containing FAEE. Cell proliferation was measured by [methyl-3H]thymidine incorporation. Protein synthesis was determined using l-[35S]methionine. Results: Incubation of cells with 600 μmol/L ethyl oleate or 800 μmol/L ethyl arachidonate decreased [methyl-3H]thymidine incorporation into HepG2 cells by 31% and 37%, respectively. LDL reconstituted with 400 μmol/L ethyl oleate decreased protein synthesis in intact HepG2 cells by 41%. Electron microscopy revealed significant changes in cell morphology, particularly involving the cell nucleus. FAEE delivered in reconstituted LDL were rapidly hydrolyzed and the fatty acids re-esterified into phospholipids, triglycerides, and cholesterol esters, with preference for triglycerides. Conclusions: These findings provide evidence that FAEE are toxic for intact human hepatoblastoma cells and that they or their metabolites may be an important causative agent in ethanol-induced liver damage.

Original languageEnglish (US)
Pages (from-to)515-522
Number of pages8
JournalGastroenterology
Volume108
Issue number2
DOIs
StatePublished - 1995
Externally publishedYes

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Hepatoblastoma
Esters
Fatty Acids
Cell Proliferation
LDL Lipoproteins
Hep G2 Cells
Ethanol
Proteins
Thymidine
Triglycerides
Cholesterol Esters
Poisons
Cell Nucleus
Methionine
Cultured Cells
Phospholipids
Electron Microscopy
Lipids
Liver

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Fatty acid ethyl esters decrease human hepatoblastoma cell proliferation and protein synthesis. / Szczepiorkowski, Zbigniew M.; Richard Dickersin, G.; Laposata, Michael.

In: Gastroenterology, Vol. 108, No. 2, 1995, p. 515-522.

Research output: Contribution to journalArticle

Szczepiorkowski, Zbigniew M. ; Richard Dickersin, G. ; Laposata, Michael. / Fatty acid ethyl esters decrease human hepatoblastoma cell proliferation and protein synthesis. In: Gastroenterology. 1995 ; Vol. 108, No. 2. pp. 515-522.
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abstract = "Background/Aims: Fatty acid ethyl esters (FAEEs) are nonoxidative products of ethanol metabolism. They have been implicated as mediators of ethanol-induced organ damage because FAEE and FAEE synthase have been found specifically in the organs damaged by ethanol abuse. This study showed toxicity specifically related to FAEE or their metabolites for intact human hepatoblastoma-derived cells (HepG2). Methods: The lipid core of human low-density lipoprotein (LDL) was extracted and the LDL particle reconstituted with either ethyl oleate or ethyl arachidonate. Cultured HepG2 cells were incubated with LDL containing FAEE. Cell proliferation was measured by [methyl-3H]thymidine incorporation. Protein synthesis was determined using l-[35S]methionine. Results: Incubation of cells with 600 μmol/L ethyl oleate or 800 μmol/L ethyl arachidonate decreased [methyl-3H]thymidine incorporation into HepG2 cells by 31{\%} and 37{\%}, respectively. LDL reconstituted with 400 μmol/L ethyl oleate decreased protein synthesis in intact HepG2 cells by 41{\%}. Electron microscopy revealed significant changes in cell morphology, particularly involving the cell nucleus. FAEE delivered in reconstituted LDL were rapidly hydrolyzed and the fatty acids re-esterified into phospholipids, triglycerides, and cholesterol esters, with preference for triglycerides. Conclusions: These findings provide evidence that FAEE are toxic for intact human hepatoblastoma cells and that they or their metabolites may be an important causative agent in ethanol-induced liver damage.",
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