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Copper distribution and incorporation into ceruloplasmin and other plasma proteins in mice overexpressing ATP7A
Author(s) -
Chu YuHsiang,
Ho Tiffinie,
Llanos Roxana,
Mercer Julian,
Linder Maria C.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.727.5
Subject(s) - atp7a , ceruloplasmin , copper , endosome , menkes disease , chemistry , medicine , endocrinology , hepatocyte , biology , atpase , biochemistry , enzyme , copper metabolism , intracellular , in vitro , organic chemistry
ATP7A is a copper pump located in the Golgi apparatus, endosomes and occasionally also on the plasma membrane of most mammalian cells except those of the liver. It is important not only for intestinal copper absorption but can remove an excess of the metal from certain cells. Transgenic mice expressing 5‐10‐fold higher levels of hATP7A over the endogenous protein were developed and used for studies of copper transport and incorporation into plasma proteins with tracer 64 Cu. As determined by native PAGE and immunoprecipitation, 64 Cu rapidly appeared in plasma ceruloplasmin after i.p. injection, and its detection is this protein was much more rapid than in rats. Although portions of mouse liver now expressed ATP7A in addition to ATP7B, there was no enhancement 64 Cu incorporation into ceruloplasmin compared to the wild type. There also was no difference in the initial distribution of radiotracer among organs, including the lactating mammary gland and milk. However, levels of actual copper in mammary gland and milk were about 40% less than in the wild type. Thus enhanced expression of ATP7A does not alter rates of copper uptake by cells from the blood plasma proteins to which it initially binds; and excess ATP7A in mammary gland does not enhance entry of copper into milk but rather pumps it back into the blood. Supported by PHS Grant No. RO1 HD 46949.