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Copper Deficiency Increases Hepatic Apolipoprotein A-I Synthesis and Secretion but Does Not Alter Hepatic Total Cellular Apolipoprotein A-I mRNA Abundance in Rats^1,2,3,

Department of Nutritional Sciences, University of Arizona, Tucson, AZ 85721

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 µmol Cu/kg diet) and copper-deficient (9.0 µmol 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.

KEY WORDS: • liver parenchymal cells • apolipoprotein A-I • apolipoprotein A-I mRNA abundance • copper • rats

¹ Presented in part at the 1992 Annual Meeting of the Federation of American Societies for Experimental Biology, April 1992, Anaheim, CA [Hoogeveen, C.A.J.M. & Lei, K. Y. (1992) Effect of copper deficiency on apolipoprotein A-I synthesis by isolated liver parenchymal cells from rats. FASEB J. 6: A1106 (abs.)] and in the AIN Graduate Student Research Award Abstract Competition at Experimental Biology 94, April 1994, Anaheim, CA (Award recipient Ron C.A.J.M. Hoogeveen) [Hoogeveen, C.A.J.M., Reaves, S. K. & Lei, K. Y. (1994) Hepatic apolipoprotein A-I gene expression in copper-deficient rats. FASEB J. 8: A818 (abs.)].

² Supported by USDA Human Nutrition Competitive Grants Program (89-37200-4423; 92-37200-7579) and funds from the University of Arizona Agricultural Experiment Station.

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ Current address: Department Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.

⁵ To whom correspondence and reprint requests should be addressed.

Manuscript received 6 April 1995. Revision accepted 25 July 1995.