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Chronic alcohol intake reduces retinoic acid concentration and enhances AP‐1 (c‐Jun and c‐Fos) expression in rat liver
Author(s) -
Wang XiangDong,
Liu Chun,
Chung Jayong,
Stickel Felix,
Seitz Helmut K.,
Russell Robert M.
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510280321
Subject(s) - retinoic acid , c jun , alcohol , chemistry , c fos , medicine , endocrinology , biochemistry , gene expression , gene , transcription factor
Chronic ethanol intake may interfere with retinoid signal transduction by inhibiting retinoic acid synthesis and by enhancing activator protein‐1 (AP‐1) (c‐Jun and c‐Fos) expression, thereby contributing to malignant transformation. To determine the effect of ethanol on hepatic retinoid levels, retinoic acid receptors (RARs) and AP‐1 (c‐Jun and c‐Fos) gene expression, chronic ethanol (36% of total calorie intake) pair‐feeding was conducted on rats for a 1‐month period. Retinoic acid, retinol, and retinyl ester concentrations in both liver and plasma were examined by using high‐performance liquid chromatography (HPLC). Both retinoic acid receptor (α, β, γ) and AP‐1 (c‐Jun and c‐Fos) expression in the rat liver were examined by using Western blot analysis. Treatment with high‐dose ethanol led to a significant reduction of retinoic acid concentration in both the liver and the plasma (11‐ and 8.5‐fold reduction, respectively), as compared with animals pair‐fed an isocaloric control diet containing the same amount of vitamin A. Similar to the retinoic acid reductions, both retinol and retinyl palmitate levels in the livers of the alcohol‐fed group decreased significantly, but in smaller fold reduction (6.5‐ and 2.6‐fold reduction, respectively). Ethanol did not modulate the expression of RARα, ‐β, and ‐γ genes in the liver. However, chronic alcohol feeding enhanced AP‐1 (c‐Jun and c‐Fos) expression by 7‐ to 8‐fold, as compared with the control group. These data suggest that functional down‐regulation of RARs by inhibiting biosynthesis of retinoic acid and up‐regulation of AP‐1 gene expression may be important mechanisms for causing malignant transformation by ethanol.