Expression and Cytoskeletal Association of Integrin Subunits Is Selectively Increased in Rat Perivenous Hepatocytes After Chronic Ethanol Administration

• Published in: Alcoholism, clinical and experimental research Vol. 25; no. 12; pp. 1749 - 1757
• Main Authors: Schaffert, Courtney S., Sorrell, Michael F., Tuma, Dean J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2001; Lippincott Williams & Wilkins
• Subjects: Alcoholic Liver Disease; Alcoholism - metabolism; Alcoholism - pathology; Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Cell Adhesion; Cells, Cultured; Collagen Type IV; Cytoskeleton; Cytoskeleton - chemistry; Cytoskeleton - metabolism; Electrophoresis, Polyacrylamide Gel; Epidermal Growth Factor Receptor; Ethanol - administration & dosage; Extracellular Matrix - metabolism; Gene Expression - drug effects; Hepatic Veins; Hepatocytes; Hepatocytes - metabolism; Hepatocytes - ultrastructure; Immunoblotting; Integrins; Integrins - genetics; Liver - blood supply; Male; Medical sciences; Rats; Rats, Wistar; Receptor, Epidermal Growth Factor - metabolism; Toxicology; Ethanol; Rat; Digestive system; Toxicity; Alcoholism; Liver; Rodentia; Hepatic disease; Gene expression; Vertebrata; Mammalia; Epidermal growth factor; Integrin; Hepatocyte; Actin; Animal; Vinculin; Digestive diseases; Genetics; Cytoskeleton; Mechanism of action; Biological receptor
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/j.1530-0277.2001.tb02186.x

Background: For normal function and survival, hepatocytes require proper cell–extracellular matrix (ECM) contacts mediated by integrin receptors and focal adhesions. Previous studies have shown that chronic ethanol consumption selectively impairs perivenous (PV) hepatocyte attachment and spreading on various ECM substrates but increases expression of the β1 integrin subunit, the common β subunit for two major hepatocyte‐ECM receptors, α1β1 and α5β1 integrins. This study examined the effects of ethanol treatment on the expression and cytoskeletal distribution of α1, α5, and β1 integrin subunits, the epidermal growth factor receptor (EGF‐R), and the cytoskeletal proteins focal adhesion kinase, paxillin, vinculin, and actin in periportal and PV hepatocytes. Methods: Periportal and PV hepatocytes were isolated from control and ethanol‐fed rats. For expression analysis, lysates were examined by SDS‐PAGE and immunoblotting procedures. For cytoskeletal distribution studies, Triton‐soluble and ‐insoluble (cytoskeletal) fractions from hepatocytes cultured on collagen IV were analyzed by SDS‐PAGE and immunoblotting. Results: Chronic ethanol administration caused PV‐specific increases in expression and cytoskeletal association of the integrin subunits. Although ethanol treatment did not affect expression of the EGF‐R in either cell type, it did increase the association of the EGF‐R with the cytoskeleton selectively in PV hepatocytes. Ethanol treatment had no significant effect on either the expression or the cytoskeletal distribution of focal adhesion kinase, paxillin, vinculin, or actin in either cell type. Conclusions: The increases in integrin expression and cytoskeletal association observed after chronic ethanol administration suggest that a process downstream of integrin‐ECM interactions is impaired selectively in PV hepatocytes, possibly involving altered focal adhesion assembly or turnover, processes essential for efficient cell‐ECM adhesion. Alterations in these processes could contribute to the impaired hepatocyte function and structure observed after chronic ethanol administration.