Radioautographic study on the intracellular localization of a hypolipidemic agent, bezafibrate, a peroxisome proliferator, in cultured rat hepatocytes.

In order to demonstrate the intracellular localization of the peroxisome proliferator in the hepatocytes, we have examined the localization of silver grains due to 14C-labelled bezafibrate in cultured rat hepatocytes by means of light and electron microscopic radioautography. As it results from the difference between chemical fixation and freeze-substitution by light microscopic radioautography, more numerous silver grains, about twice, were observed in freeze-substitution specimens in comparison with chemical fixation. On light microscopic radioautograms of the epoxy resin sections during each experimental condition, about 90% of all the silver grains were localized over the cytoplasm. Then, statistical significance was evaluated on grain density in the cytoplasm. On electron microscopic radioautograms of whole mount cultured cells, silver grains were localized not on the peroxisome but on the cytoplasmic matrix specially over the endoplasmic reticulum. From these results, it is concluded that bezafibrate was localized over endoplasmic reticulum. This fact suggests that the receptor of the peroxisome proliferator should be associated with the endoplasmic reticulum or that the receptor exists on the endoplasmic reticulum. Thus, it is demonstrated that the peroxisome proliferator acts on the endoplasmic reticulum of hepatocytes to proliferate peroxisomes.