VESICLE MOVEMENT IN RAT HEPATOCYTES IS REDUCED BY ETHANOL EXPOSURE - ALTERATIONS IN MICROTUBULE-BASED MOTOR ENZYMES

Background & Aims: Ethanol is known to alter vesicle-mediated protein trafficking in hepatocytes by undefined mechanisms. In this study, the effects of long- and short-term ethanol exposure on vesicle movements were measured in isolated hepatocytes, and alterations in the functio n of the microtubule-associated motor enzymes dynamin, kinesin, and dy nein, which are believed to support the transport and/or budding of ve sicles along microtubules, were tested. Methods: Vesicular movements i n isolated hepatocytes exposed to short- and long-term ethanol treatme nt were measured. Motor adenosine triphosphatase activities and their association with specific membrane organelles were assessed in respons e to long-term administration of ethanol in vivo or acetaldehyde in vi tro. Results: Hepatocytes exposed to short- or long-term ethanol treat ment showed a significant reduction in the number of motile vesicles. No alterations in the levels of motor messenger RNA, protein, or enzym atic activity were observed. Interestingly, ethanol had no effect on t he association of dynein and kinesin with membranes, whereas there was a significant increase in the amount of dynamin associated specifical ly with Golgi membranes. Conclusions: Long- and short-term ethanol exp osure markedly reduces hepatocellular vesicle transport by a mechanism apparently independent of any alteration in the enzymatic activity of molecular motors, possibly involving a change in the function of dyna min.