The regulation of apolipoprotein A-I gene expression: Dietary copper and zinc
AuthorWu, Yongjian, 1969-
AdvisorLei, David K. Y.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractCopper (Cu) deficiency was induced in rats and Hep G2 cells by the use of a Cu-deficient diet and a cupruretic chelator, respectively. In the rat liver, Cu-deficiency did not alter the apo A-I mRNA abundance, but shifted significant amounts of mRNA to translationally more active fractions. These findings indicated that an increase in translational efficiency may contribute to the increase in hepatic apo A-I synthesis observed in Cu-deficient rats. In Hep G2 cells, Cu-depletion elevated the cytoplasmic apo A-I mRNA abundance by 1.5-fold. A 2.5-fold increased transcription rate and a 2-fold accelerated mRNA decay were also established in Cu-depleted cells. These changes appeared to be specific to Cu depletion, because they were reversed by Cu repletion. Moreover, the cytoplasmic mRNA abundance of HNF-4, a major transcription activator of apo A-I gene, was elevated by 1.6-fold in Cu-depleted cells. Thus the elevated cellular apo A-I mRNA level may have resulted from an accelerated mRNA turnover, and subsequently contributed to the enhanced apo A-I synthesis and secretion observed in Cu-depleted cells. Zinc (Zn) deficiency was induced in animals and Hep G2 cells by the use of Zn-deficient diet and medium, respectively. Plasma HDL apo A-I levels was reduced 18% in hamsters and 13% in rats. Whereas Zn repletion normalized plasma apo A-I to the control level in hamsters and increased it by 34% in rats. No treatment difference was detected in the intestinal apo A-I mRNA abundance in both species, although the hepatic abundance was reduced by 18% and 55% in Zn-deficient hamsters and rats, respectively. Subsequent Zn-repletion normalized the mRNA abundance to the control level in hamsters and elevated it by 41% in rats. As compared to control Hep G2 cells, the cellular Zn content and apo A-I mRNA abundance were reduced by 55% and 20% in Zn-depleted cells, but increased by 64% and 11% in Zn-supplemented cells, respectively. Furthermore, Zn-repletion completely normalized the effects of Zn-depletion. Thus the depletion of hepatic Zn content may cause the reductions in hepatic apo A-I mRNA abundance and plasma apo A-I pool observed in Zn deficiency.
Degree ProgramGraduate College