Abstract：
:The copper-transporting ATPases Atp7A and Atp7B play a major role in controlling intracellular copper levels. In addition, they are believed to deliver copper to the copper-requiring proteins destined for the secretory vesicles. One cuproprotein, dopamine beta-hydroxylase (DBH) functions in the biosynthesis of norepinephrine and epinephrine, neurohormones in endocrine and nervous tissue. To evaluate the consequences of loss of Atp7B on the function of DBH, the level of proteins in adrenal gland were compared between normal mice and mice containing a null mutation in the ATP7B gene. The levels of DBH, as well as another vesicular protein, chromogranin A, are reduced in the ATP7B -/- mice. In addition to the lower level of enzyme, the products of DBH catalytic activity, norepinephrine and epinephrine, are also decreased. Although these changes are a consequence of ATP7B gene function, Atp7B mRNA is not normally expressed in the adrenal gland. Instead, Atp7A mRNA is present. The levels of copper and DBH RNA within adrenals of the ATP7B -/- mice are not different from the wild type. The results of these experiments suggest that copper-requiring enzymes are affected by a loss of ATP7B even in tissue not normally expressing this protein. Therefore the multisystemic effects observed in Wilson disease, the human disorder characterized by mutation in ATP7B, may be a secondary consequence of the major accumulation of copper in liver.
journal_name
Neurochem Resjournal_title
Neurochemical researchauthors
Gerbasi V,Lutsenko S,Lewis EJdoi
10.1023/a:1023219308890keywords:
subject
Has Abstractpub_date
2003-06-01 00:00:00pages
867-73issue
6eissn
0364-3190issn
1573-6903journal_volume
28pub_type
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