Effect of chelators on copper metabolism and copper pools in mouse hepatocytes

Journal Article · Sat Apr 01 00:00:00 EST 1989 · Am. J. Physiol.; (United States)

OSTI ID:5985679

McArdle, H J; Gross, S M; Creaser, I; Sargeson, A M; Danks, D M

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 /sup 64/Cu 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.

• Research Organization: Royal Children's Hospital, Melbourne, Victoria (Australia)
• OSTI ID: 5985679
• Journal Information: Am. J. Physiol.; (United States), Vol. 256
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
CHELATING AGENTS
BIOLOGICAL EFFECTS
COPPER
METABOLISM
COPPER 64
HETEROCYCLIC COMPOUNDS
LIVER CELLS
MICE
PENICILLAMINE
TRACER TECHNIQUES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
COPPER ISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
HOURS LIVING RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
METALS
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RODENTS
SOMATIC CELLS
THIOLS
TRANSITION ELEMENTS
VERTEBRATES
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