Copper deficiency increases hepatic apolipoprotein A-I synthesis and secretion but does not alter hepatic total cellular apolipoprotein A-I mRNA abundance in rats.
This study was designed to determine whether an increase in hepatic apolipoprotein A-I (apo A-I) synthesis and mRNA abundance is responsible for the enlarged plasma apo A-I pool observed in copper-deficient rats. Weanling male Sprague-Dawley rats were divided into two dietary treatments: copper-adequate (102.2 mumol Cu/kg diet) and copper-deficient (9.0 mumol Cu/kg diet). Copper deficiency resulted in a significant increase (124%) in intravascular apo A-I pool size after 6 wk of treatment. Following intraportal injection of a flooding dose of [3H]phenylalanine, in vivo hepatic apo A-I synthesis and secretion were significantly greater in the copper-deficient animals as detected by [3H]phenylalanine incorporation into immunoprecipitable apo A-I isolated from liver homogenates and plasma using anti-rat apo A-I antibodies. Pulse-chase experiments using freshly isolated hepatocytes demonstrated that a significant increase (148%) in apo A-I secretion by hepatocytes derived from copper-deficient rats may have resulted from increased hepatic synthesis rather than altered intracellular degradation of apo A-I. Hepatic total cellular apo A-I mRNA abundance was not altered by copper deficiency when expressed per microgram of RNA. Thus, the enhanced hepatic apo A-I synthesis, observed in copper-deficient cells, may have resulted from alterations in post-transcriptional and translational processes.
D000596:Amino Acids / Q000032:analysis / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern; D003300:Copper / Q000172:deficiency*; D004247:DNA / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010649:Phenylalanine / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
D000596:Amino Acids; D016632:Apolipoprotein A-I; D012333:RNA, Messenger; D014316:Tritium; D010649:Phenylalanine; D003300:Copper; D004247:DNA