Induction of Ceruloplasmin Synthesis by Retinoic Acid in Rats: Influence of Dietary Copper and Vitamin A Status

Abstract

Ceruloplasmin, a copper-containing acute phase plasma protein, has been shown to be regulated by 13-cis retinoic acid in rats. Ceruloplasmin activity was significantly increased within 24 h and remained elevated for at least 72 h after a single injection of 13-cis retinoic acid. With daily injections of retinoic acid, the ceruloplasmin activity continued to increase for at least 4 d. After 4 d, the activity was four times control levels. In copper-deficient rats, the ceruloplasmin activity did not increase in response to retinoic acid unless copper was also given to these rats 8 h after retinoic acid. Actinomycin D blocked the retinoic acid—induced stimulation of ceruloplasmin activity in copper-sufficient rats, but in copper-deficient rats only about half of the increase was blocked when the rats were given copper or copper and retinoic acid. By use of pulse-labeling techniques, ceruloplasmin synthesis was shown to increase 1.5-fold after retinoic acid and this increase was blocked by actinomycin D. When vitamin A—deficient rats were repleted with 13-cis retinoic acid for 3 or 5 d, both the ceruloplasmin activity and synthesis were significantly stimulated when compared to the nonrepleted, deficient rats. Therefore, the dietary components, copper and vitamin A, play an important role in the regulation of plasma ceruloplasmin levels.