Short-term effects of carbon tetrachloride on the lipoprotein secretion in isolated rat hepatocytes

Summary

Short-term exposure of isolated rat hepatocytes in suspension to a low dose of CC1⁴ (20 μg/ml) leads within minutes to characteristic structural alterations. The earliest reaction is a disappearance of the microvilli border 5 min after starting the incubation. After 10 min the number of Golgi VLDL is decreased by about 80% and reaches zero after 20 min. The reduction in Golgi VLDL is associated with a decrease in the volume density of the Golgi complexes by about 50% compared with controls and by a marked elevation of intracytoplasmic and intralysosomal lipid deposits after 20 min incubation. Concomitantly with these alterations the total number of VLDL particles within single and multiple particle secretory vesicles located along the cell periphery decreases by about 50% 10 min after CC1₄ exposure. This is followed 10 min later by a significant increase of about 20% compared with the corresponding controls. The elevation in the total number of VLDL is combined with an increase in the number of the multiple particle secretory vesicles. The particle content per vesicle, however, is significantly lower compared with controls. No reaction is detectable in the mitochondria, whereas the amount of RER appears to be decreased and that of the SER increased. The incubation of¹⁴C-sodium palmitate prelabeled hepatocytes in the presence of CC1₄ leads to a significantly higher content of labeled lipids in the total Golgi fraction and in the cytosol 20 min after CC1₄ administration, whereas considerably less labeled lipids are secreted into the incubation medium. Our morphological and biochemical findings suggest that within the VLDL-TG secretory pathway the first step (coupling of lipids to apoproteins) and the last step (exocytosis of VLDL) are rapidly affected by CC1₄, whereas step 3 (packaging and transporting of those VLDL processed just before the CC1₄ intoxication) appears not to be impaired immediately.