Effects of ethanol, acetaldehyde, and lactate on proteoglycan synthesis and proliferation of cultured rat liver fat-storing cells.
The hypothesis that ethanol and some of its metabolites are directly involved in the process of fat-storing cell activation and stimulated proteoglycan synthesis in alcoholic liver injury was investigated. The effects of short-term (24 h) and long-term (4 days) exposure of rat liver fat-storing cells at various times of culture to ethanol, acetaldehyde, and lactate on the synthesis of proteoglycans and total protein and on the proliferation activity of the cells were studied. Ethanol and lactate did not stimulate the incorporation of [35S]sulfate into glycosaminoglycans. Acetaldehyde inhibited strongly glycosaminoglycan synthesis, reaching 50% inhibition at 330 mumol/L. The compound preferentially inhibited the synthesis of dermatan sulfate. No significant changes of glycosaminoglycan chain length or of the degree of polysaccharide sulfation were noted in acetaldehyde-treated cultures. The inhibition was reversed by the addition of beta-D-xylopyranoside (0.5 mmol/L), an artificial initiator of chain elongation, to the medium. Total protein synthesis, cell number, deoxyribonucleic acid content of the cultures, and [3H]thymidine incorporation were not affected by the compounds. The results do not support the view that ethanol, its oxidation product acetaldehyde, or lactate are directly involved in the activation of fat-storing cells and in enhanced matrix proteoglycan synthesis and secretion.
Gressner
A M
AM
Abteilung für Klinische Chemie, Philipps-Universität, Marburg, Federal Republic of Germany.
Althaus
M
M
D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D000431:Ethanol / Q000494:pharmacology*; D005223:Fats / Q000378:metabolism; D007773:Lactates / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011509:Proteoglycans / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D005223:Fats; D007773:Lactates; D011509:Proteoglycans; D000431:Ethanol; D000079:Acetaldehyde