Evidence that microtubules play a permissive role in hepatocyte very low density lipoprotein secretion.
To determine whether a minimum number of assembled microtubules is required for very low density lipoprotein (VLDL) triglyceride TG) secretion in hepatocytes, antimicrotubule drugs of different concentrations were given to rats. Hepatic VLDL-TG release was subsequently measured by a liver perfusion system, and hepatocyte ultrastructural changes were analyzed by quantitative ultrastructural methods. The results demonstrate a tight coupling between the reduction in hepatocyte microtubule content and the reduction in hepatic VLDL-TG secretion which is related to the dose of colchicine or vinblastine administered. The various estimates imply that a minimum number of microtubules is necessary for hepatic VLDL secretion to proceed normally and that hepatic VLDL secretion rates reach their nadir (10--30% of control) when microtubules comprise less than 0.005% of the cytoplasm (or less than 10% of control values) when microtubules comprise less than 0.005% of the cytoplasm (or less than 10% of control values). At this point, hepatocyte Golgi complexes are also greatly altered; Golgi complexes with recognizable dictyosomal membranes are reduced to 15% of control values and the region is filled with large numbers of electron-dense bodies which appear to be lysosomes in the process of digesting VLDL. There is a predilection for the remaining Golgi complexes to be associated with a few segments of microtubules, even when no microtubules can be measured in random samplings of hepatocytes. Clusters of vacuoles containing VLDL are also present throughout the cytoplasm; the limiting membranes of 25% of these vacuoles are studded with ribosomes. These findings demonstrate that the administration of antimicrotubule agents results in decreases in hepatic VLDL-TG secretion which are associated with loss of microtubules and alteration of existing Golgi complexes.
D000818:Animals; D003078:Colchicine / Q000494:pharmacology; D006056:Golgi Apparatus / Q000648:ultrastructure; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008247:Lysosomes / Q000648:ultrastructure; D008297:Male; D008870:Microtubules / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D014280:Triglycerides / Q000378:metabolism*; D014747:Vinblastine / Q000494:pharmacology
D008079:Lipoproteins, VLDL; D014280:Triglycerides; D014747:Vinblastine; D003078:Colchicine