COPPER DEFICIENCY INCREASES HEPATIC APOLIPOPROTEIN-A-I SYNTHESIS AND SECRETION BUT DOES NOT ALTER HEPATIC TOTAL CELLULAR APOLIPOPROTEIN-A-IMESSENGER-RNA ABUNDANCE IN RATS

This study was designed to determine whether an increase in hepatic ap olipoprotein A-I (ape A-I) synthesis and mRNA abundance is responsible for the enlarged plasma apo A-I pool observed in copper-deficient rat s. Weanling male Sprague-Dawley rats were divided into two dietary tre atments: copper-adequate (102.2 mu mol Cu/kg diet) and copper-deficien t (9.0 mu mol Cu/kg diet). Copper deficiency resulted in a significant increase (124%) in intravascular apo A-I pool size after 6 wk of trea tment. Following intraportal injection of a flooding dose of [H-3]phen ylalanine, in vivo hepatic apo A-I synthesis and secretion were signif icantly greater in the copper-deficient animals as detected by [H-3]ph enylalanine incorporation into immunoprecipitable apo A-I isolated fro m liver homogenates and plasma using anti-rat apo A-I antibodies. Puls e-chase experiments using freshly isolated hepatocytes demonstrated th at a significant increase (148%) in apo AI secretion by hepatocytes de rived from copper-deficient rats may have resulted from increased hepa tic synthesis rather than altered intracellular degradation of apo A-I . Hepatic total cellular apo A-I mRNA abundance was not altered by cop per deficiency when expressed per microgram of RNA. Thus, the enhanced hepatic apo A-I synthesis, observed in copper-deficient cells, may ha ve resulted from alterations in post-transcriptional and translational processes.