Time course of ethanol-induced impairment in fluid-phase endocytosis in isolated rat hepatocytes

Authors

  • Kenneth B. Camacho,

    1. Liver Study Unit, Department of Veterans Affairs Medical Center, University of Nebraska Medical Center, Omaha, Nebraska 68105
    2. Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68105
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  • Carol A. Casey,

    1. Liver Study Unit, Department of Veterans Affairs Medical Center, University of Nebraska Medical Center, Omaha, Nebraska 68105
    2. Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68105
    3. Department of Biochemistry, University of Nebraska Medical Center, Omaha, Nebraska 68105
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  • Robert L. Wiegert,

    1. Liver Study Unit, Department of Veterans Affairs Medical Center, University of Nebraska Medical Center, Omaha, Nebraska 68105
    2. Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68105
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  • Michael F. Sorrell,

    1. Liver Study Unit, Department of Veterans Affairs Medical Center, University of Nebraska Medical Center, Omaha, Nebraska 68105
    2. Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68105
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  • Dean J. Tuma Ph.D.

    Corresponding author
    1. Liver Study Unit, Department of Veterans Affairs Medical Center, University of Nebraska Medical Center, Omaha, Nebraska 68105
    2. Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68105
    3. Department of Biochemistry, University of Nebraska Medical Center, Omaha, Nebraska 68105
    • Liver Study Unit (151), Veterans Affairs Medical Center, 4101 Woolworth Ave., Omaha, NE 68105
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Abstract

The time-course effects of long-term ethanol administration on fluid-phase endocytosis were studied in isolated rat hepatocytes. Rats were pair-fed an ethanol-supplemented liquid diet or an isocaloric control diet for 3 days, 1 wk, 2 wk or 5 wk. Hepatocytes were isolated and incubated at 37° C with various concentrations of the fluid-phase marker Lucifer yellow.-Net internalization of the marker dye was determined. After as little as 1 wk, ethanol-fed rats demonstrated marked decreases in the net internalization of dye compared with pair-fed controls; these changes persisted throughout 5 wk of feeding. Because net internalization is the balance between uptake into the cells vs. efflux from the cells, these components were examined individually. Early uptake was not significantly decreased by ethanol feeding; however, efflux of preloaded Lucifer yellow from cells from the ethanol-fed animals was markedly faster than efflux from pair-fed controls. This increased efflux was more prominent in the longer preload time (90 min) compared with a shorter preload time (15 min), indicating an alteration in dye distribution among various intracellular pools. These ethanol-induced changes in fluid-phase endocytosis were apparent for 1 wk through 5 wk of feeding and were similar for all Lucifer yellow concentrations examined. These results indicate that the decreased net internalization of Lucifer yellow through fluid-phase endocytosis is mainly a result of an ethanol-induced increase in efflux possibly caused by altered intracellular trafficking rather than by reduction in uptake. (HEPATOLOGY 1993;17:661–667.)

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