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International Journal of Hepatology
Volume 2012 (2012), Article ID 954157, 5 pages
http://dx.doi.org/10.1155/2012/954157
Research Article

Cyanamide Potentiates the Ethanol-Induced Impairment of Receptor-Mediated Endocytosis in a Recombinant Hepatic Cell Line Expressing Alcohol Dehydrogenase Activity

1Liver Study Unit, Department of Veterans’ Affairs, Omaha, NE 68105, USA
2Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA

Received 30 July 2011; Accepted 16 November 2011

Academic Editor: Kusum Kharbanda

Copyright © 2012 Dahn L. Clemens et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Ethanol administration has been shown to alter receptor-mediated endocytosis in the liver. We have developed a recombinant hepatic cell line stably transfected with murine alcohol dehydrogenase cDNA to serve as an in vitro model to investigate these ethanol-induced impairments. In the present study, transfected cells were maintained in the absence or presence of 25 mM ethanol for 7 days, and alterations in endocytosis by the asialoglycoprotein receptor were determined. The role of acetaldehyde in this dysfunction was also examined by inclusion of the aldehyde dehydrogenase inhibitor, cyanamide. Our results showed that ethanol metabolism impaired internalization of asialoorosomucoid, a ligand for the asialoglycoprotein receptor. The addition of cyanamide potentiated the ethanol-induced defect in internalization and also impaired degradation of the ligand in the presence of ethanol. These results indicate that the ethanol-induced impairment in endocytosis is exacerbated by the inhibition of aldehyde dehydrogenase, suggesting the involvement of acetaldehyde in this dysfunction.