EFFECT OF HEPATOCYTE SWELLING ON MICROTUBULE STABILITY AND TUBULIN MESSENGER-RNA LEVELS

Incubation of isolated rat hepatocytes under conditions known to induc e cell swelling caused several alterations in microtubule physiology. As shown by immunofluorescence microscopy experiments in the absence a nd presence of triethyllead or colchicine (two well-established microt ubule inhibitors), an apparent stabilization of the microtubule networ k became evident in hepatocytes exposed to hypotonic (190 mosmol/L) co nditions. A similar stabilizing effect was also observed upon cell swe lling induced by addition of insulin (100 nmol/L) or glutamine (10 mmo l/L). The differential microtubule stabilities were not attributed to a differential incorporation of the antimicrotubular agents into hepat ocytes as shown by [H-3]colchicine-uptake experiments. The swelling-in duced alterations of microtubules may contribute to the swelling-induc ed changes of liver cell function: in perfused rat liver it was found that the established inhibitory effect of hypotonic cell swelling on h epatic proteolysis was largely abolished in presence of colchicine. Tu bulin mRNA levels increased by 1.9-, 2.1- and 2.7-fold in isolated hep atocytes being exposed for 120 min to hypotonic medium, insulin, or gl utamine, respectively. The results suggest an involvement of microtubu lar structures in the regulation of liver metabolism in response to al terations of the cellular hydration state.