Ligands maintain cytochrome P-450 in liver cell culture by affecting its synthesis and degradation

Abstract

Rat hepatocytes cultured for 24 h lose 68% of their cytochrome P-450. It is shown that this loss is due to the failure of cultured hepatocytes to synthesize cytochrome P-450 as well as enhanced degradation. Compounds that form ligands with cytochrome P-450, eg metyrapone, prevent the loss of cytochrome P-450. Ligands are generally considered to protect proteins from degradation but the present work suggests that the effect of metyrapone on cytochrome P-450 synthesis is of equal importance to its effect on degradation in preventing the loss of cytochrome P-450 in hepatocyte culture.