AJP - Gastrointestinal and Liver Physiology, Vol 256, Issue 4 667-G672, Copyright © 1989 by American Physiological Society
Effect of chelators on copper metabolism and copper pools in mouse hepatocytes
H. J. McArdle, S. M. Gross, I. Creaser, A. M. Sargeson and D. M. Danks
Murdoch Institute for Research into Birth Defects, Royal Children's Hospital, Melbourne, Victoria.
Disorders of copper storage are usually treated by chelation therapy. It is
generally thought that the chelators act by mobilizing copper from the
liver, hence allowing excretion in the urine. This paper has examined the
effect of chelators on copper uptake and storage in mouse hepatocytes.
Penicillamine, a clinically important chelator, does not block the uptake
of copper or remove copper from hepatocytes. Two other copper chelators,
sar and diamsar, which form very stable and kinetically inert Cu2+
complexes by encapsulating the metal ion in an organic cage, were shown to
block copper accumulation by the cells and to remove up to 80% of
cell-associated copper. They also removed most (approximately 80%) of the
64Cu accumulated by the cells in 30 min, but released only a small
percentage (less than 20%) of that accumulated over 18 h. The results show
that copper in the hepatocyte can be divided into at least two pools, an
easily accessible one, and another, not removable even after long-term
incubation with any of the chelators. Most of the copper normally found in
the cell appeared to be associated with the former pool.
