Effect of the glutathione-depleting agents diethylmaleate, phorone and buthionine sulfoximine on biliary copper excretion in rats

Nederbragt, H.

doi:10.1016/0006-2952(89)90107-x

Cited by 14 publications

(2 citation statements)

References 24 publications

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“…The tripeptide glutathione (GSH) is present at high concentration in a number of tissues [69], and has been shown to bind Cu(I) and to play a role in biliary excretion of copper [70,71]. In addition, GSH can transfer copper to cuproproteins including metallothioneins [72][73][74], a family of proteins that play an important role in metal detoxification.…”

Section: Gsh and Metallothioneinsmentioning

confidence: 99%

Maintaining copper homeostasis: regulation of copper-trafficking proteins in response to copper deficiency or overload

Bertinato

L’Abbé

2004

The Journal of Nutritional Biochemistry

187

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Section: Gsh and Metallothioneinsmentioning

confidence: 99%

Maintaining copper homeostasis: regulation of copper-trafficking proteins in response to copper deficiency or overload

Bertinato

L’Abbé

2004

The Journal of Nutritional Biochemistry

187

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“…The Wilsons disease protein apparently plays a number of important roles in the hepatocyte (see Figure 2). These roles include the following: (1) the direct export of copper from the hepatocyte cytoplasm into the biliary canaliculi, (2) the facilitation of copper uptake by lysosomes prior to their fusion with the hepatocyte plasma membrane bordering the biliary canaliculi (28)(29)(30), and (3) copper import into the Golgi apparatus for insertion into nascent proteins, including ceruloplasmin (31). The Menkes disease protein would appear to carry out similar functions in nonhepatic cell lines given that little or no Menkes disease protein mRNA can be found in the liver (32,33).…”

Section: Hepatic Copper Metabolismmentioning

confidence: 99%

Molecular mechanisms of copper metabolism and the role of the Menkes disease protein

Harrison

Dameron

1999

J. Biochem. Mol. Toxicol.

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Menkes disease is an X‐linked, recessive disorder of copper metabolism that occurs in approximately 1 in 200,000 live births. The condition is characterized by skeletal abnormalities, severe mental retardation, neurologic degeneration, and patient mortality in early childhood. The symptoms of Menkes disease result from a deficiency of serum copper and copper‐dependent enzymes. A candidate gene for the disease has been isolated and designated MNK. The MNK gene codes for a P‐type cation transporting ATPase, based on homology to known P‐type ATPases and in vitro experimentation. cDNA clones of MNK in Menkes patients show diminished or absented hybridization in northern blot experiments. The Menkes protein functions to export excess intracellular copper and activates upon Cu(I) binding to the six metal‐binding repeats in the amino‐terminal domain. The loss of Menkes protein activity blocks the export of dietary copper from the gastrointestinal tract and causes the copper deficiency associated with Menkes disease. Each of the Menkes protein amino‐terminal repeats contains a conserved ‐X‐Met‐X‐Cys‐X‐X‐Cys‐ motif (where X is any amino acid). These metal‐binding repeats are conserved in other cation exporting ATPases involved in metal metabolism and in proteins involved in cellular defense against heavy metals in both prokaryotes and eukaryotes. An overview of copper metabolism in humans and a discussion of our understanding of the molecular basis of cellular copper homeostasis is presented. This forms the basis for a discussion of Menkes disease and the protein deficit in this disease. © 1998 John Wiley & Sons, Inc. J Biochem Toxicol 13: 93–106, 1999

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Biliary copper excretion in the neonatal rat: Role of glutathione and metallothionein

Mohan

Failla

Bremner³

et al. 1995

Hepatology

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Metallothionein (MT) and glutathione (GSH) have been implicated as two major copper-binding agents involved in the hepatobiliary copper metabolism in the adult rat. This study was designed to explore their potential role in facilitating copper export from the copper-laden hepatocyte of the newborn rat. Biliary and hepatic copper, GSH, and immunoreactive MT-I concentrations were measured in Sprague-Dawley rats at 1, 2, 3, 4, and 8 weeks of age. Bile was collected by duct cannulation for 90 minutes before the rats were killed. Liver was removed, weighed, and freeze-dried. The bile flow rate (BFR) doubled and the liver weight increased 14-fold during maturation. Hepatic and biliary copper and MT-I concentrations were significantly higher in the suckling than in the weanling. The total biliary output of copper per 24 hours was low at 1 week and increased significantly by 8 weeks of age. MT-I-bound copper represented a maximum of only 3.4% of biliary copper at 1 week and 0.5% at 8 weeks. GSH was not detected in bile until 2 weeks and then increased 15-fold by 8 weeks, while hepatic GSH levels remained unchanged. Therefore, GSH levels did not correlate with the high biliary copper concentration at week 1, although there was a close correlation between the total daily biliary excretion of copper and GSH at 2 weeks and beyond. We conclude that the net biliary copper excretion per day is relatively low in the first week of life and is independent of MT and GSH secretion. It increases significantly once GSH is available in bile.(ABSTRACT TRUNCATED AT 250 WORDS)

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Effect of the glutathione-depleting agents diethylmaleate, phorone and buthionine sulfoximine on biliary copper excretion in rats

Cited by 14 publications

References 24 publications

Maintaining copper homeostasis: regulation of copper-trafficking proteins in response to copper deficiency or overload

Maintaining copper homeostasis: regulation of copper-trafficking proteins in response to copper deficiency or overload

Molecular mechanisms of copper metabolism and the role of the Menkes disease protein

Biliary copper excretion in the neonatal rat: Role of glutathione and metallothionein

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