Effect of chronic ethanol administration on enzyme and lipid properties of liver plasma membranes in long and short sleep mice
✍ Scribed by Thomas Zysset; Mark A. Polokoff; Francis R. Simon
- Publisher
- John Wiley and Sons
- Year
- 1985
- Tongue
- English
- Weight
- 754 KB
- Volume
- 5
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
Mechanisms of alcoholic liver disease are still ill defined. We evaluated in two outbred lines of mice whether chronic ingestion of ethanol alters the lipid composition and/or enzyme activity of liver plasma membranes. Two mouse lines with different sensitivities towards the hypnotic effect of ethanol, designated long sleep and short sleep, were fed a liquid diet containing ethanol for 30 days. Ethanol intake reached 30 gm per kg per day in both lines, and serum ethanol levels were similar. In addition, hepatic triglyceride levels were similarly increased 2-fold with ethanol feeding. The following effects of ethanol treatment were observed in liver plasma membrane fractions: (i) Na+,K+-ATPase was significantly increased to 26% above control in long sleep only; (ii) alkaline phosphatase activity was 2-fold increased in both lines; (iii) 5'-nucleotidase, leucine aminopeptidase and Mga+-ATPase activities remained unchanged in both lines; (iv) unesterified cholesterol and total phospholipid contents were unaltered in both lines, and (v) cholesteryl esters were increased in both lines, but to a greater extent in short sleep (1.5 vs. 4-fold). Thus, chronic ethanol ingestion induces specific alterations in liver plasma membrane structure and function, suggesting that adaptive responses to ethanol may be determined in part by inherited factors.
Mechanisms leading to alcoholic liver disease are still poorly defined. In spite of the strong association between the amount and duration of ethanol ingestion and the development of liver disease, cirrhosis develops in only about 15% of alcoholics (1). Thus, it has been suggested that other factors, including hereditary predisposition (2), may also be involved in the pathogenesis of alcoholic liver disease.
Recently, it has been shown that chronic ethanol ingestion is associated with structural and functional alterations of membranes, including hepatic mitochondrial and endoplasmic reticulum membranes (3-5). Ethanol directly "fluidizes" membrane lipid bilayers, and it has been proposed that cell surface membranes may