EFFECTS OF ACETALDEHYDE ON MICROTUBULES AND HEPATIC KINESIN - A STUDYOF THE PATHOGENESIS OF ALCOHOLIC LIVER-DISEASE

In ballooned hepatocytes associated with alcoholic liver disease, secr etory proteins are abundant, possibly due to an impairment of the micr otubule-dependent vesicular transport system. We studied the effects o f ethanol and acetaldehyde on microtubules and hepatic kinesin functio n. Tubulin and microtubule-associated protein 2 was purified by phosph ocellulose and hydroxyapatite column chromatography from microtubule p roteins of bovine brain. Hepatic kinesin was purified from rabbit live r. The assembly of microtubules was quantified by spectro-photometer. The kinesin motility assay is done with or without various concentrati ons of ethanol or acetaldehyde using video-enhanced differential inter ference contrast microscopy. Ethanol had no effect on the assembly or disassembly of the microtubules or on hepatic kinesin function, even a t high concentrations of up to 100 mM. In contrast, acetaldehyde reduc ed hepatic kinesin function at concentrations greater than or equal to 100 mu M and induced microtubular disassembly at concentrations great er than or equal to 200 mu M. In alcoholic liver injury, chronic reduc tion of hepatic kinesin function may cause retention of secretory prot eins and hepatocyte swelling. Moreover, reduction of the microtubule c oncentrations due to acetaldehyde may further impair the vesicular tra nsport system and reduce the cells ability to maintain morphology, in turn accelerating hepatocyte ballooning. (C) 1998 Elsevier Science Ire land Ltd. All rights reserved.