Intracellular distribution of copper in the liver during chronic administration of copper sulfate to the rat

Lal, S.

doi:10.1016/s0041-008x(71)80009-1

Cited by 35 publications

(11 citation statements)

References 20 publications

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“…In sheep livers with elevated copper content, the proportion of copper found in the cytosol fraction increased while the proportion found in the large granule fraction decreased. This is in contrast to the results obtained with copperloaded rats where the opposite effect is observed, i.e., an increase in the proportion in the large granule fraction concomitant with a decrease in the proportion present in the cytosol fraction (Gregoriadis and Sourkes, 1967;Verity et al, 1967;Evans et al, 1970;Lal and Sourkes, 1971). However, Milne and Weswig (1968) reported a study in which no change in the distribution pattern was observed with increased hepatic copper.…”

Section: Resultscontrasting

confidence: 65%

“…It could be argued that the results obtained in these experiments are misleading because of the great difference in hepatic copper content of the two species used in these investigations. In a study of copper loading of rat liver, Lal and Sourkes (1971) concluded that the partition of copper between the large granule and nuclear fractions was a function of actual hepatic concentration. Between 30 and 100 #g Cu/g tissue, a larger proportion was found in the mitochondrial (large granule) fraction.…”

Section: Discussionmentioning

confidence: 99%

“…To determine if the above observation could be applied to our data with sheep liver, data from this study, combined with data obtained from sheep slaughtered at The Pennsylvania State University Meats Laboratory, were compared with data for individual copper-loaded rats published by Gregoriadis andSourkes (1967), Evans et al (1970) and Lal and Sourkes (1971). A summary of these data is presented in table 3.…”

Section: Discussionmentioning

confidence: 99%

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Intracellular Distribution of Hepatic Cooper in Normal and Copper-Loaded Sheep

Corbett

Saylor

Tan

et al. 1978

Journal of Animal Science

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Section: Resultscontrasting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Intracellular Distribution of Hepatic Cooper in Normal and Copper-Loaded Sheep

Corbett

Saylor

Tan

et al. 1978

Journal of Animal Science

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“…However, when copper is massively deposited in mitochondria, an intracellular competition between copper redistribution and mitochondrial damage seems to set in. On the one hand, due to the fast turnover of mitochondria in hepatocytes, their copper may be redistributed to other compartments like the lysosome or the nucleus, possibly causing copper‐related deleterious effects in these compartments . On the other hand, persistent mitochondrial copper accumulation may take place as a result of continuous copper influx into the hepatocytes and, possibly, disturbed mitochondrial turnover.…”

Section: Discussionmentioning

confidence: 99%

“…A strong line of evidence of mitochondrial participation in copper‐dependent hepatocyte death stems from copper‐feeding studies . In an electron micrograph from the liver of a rat fed a copper‐enriched diet, mitochondrial structure changed (i.e., microcystic formations at the cristae are visible after 1 week) .…”

Section: Mitochondrial Damage In Studies Mimicking Wd Conditions and mentioning

confidence: 99%

Pathological mitochondrial copper overload in livers of Wilson's disease patients and related animal models

Zischka

Lichtmannegger

2014

Annals of the New York Academy of Sciences

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In Wilson's disease (WD) and related animal models, liver mitochondria are confronted with an increasing copper burden. Physiologically, the mitochondrial matrix may act as a dynamic copper buffer that efficiently distributes the metal to its copper-dependent enzymes. Mitochondria are the first responders in the event of an imbalanced copper homeostasis, as typical changes of their structure are among the earliest observable pathological features in WD. These changes are due to accumulating copper in the mitochondrial membranes and can be reversed by copper-chelating therapies. At the early stage, copper-dependent oxidative stress does not seem to occur. On the contrary, however, when copper is massively deposited in mitochondria, severe structural and respiratory impairments are observed upon disease progression. This provokes reactive oxygen species and consequently causes the mitochondrial membranes to disintegrate, which triggers hepatocyte death. Thus, in WD mitochondria are prime targets for copper, and the excessive copper burden causes their destruction, subsequently provoking tissue failure and death.

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Strain-related patterns of biliary excretion and hepatic distribution of copper in the rat

Nederbragt

Lagerwerf

1986

Hepatology

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Biliary copper excretion was studied in male, bile-cannulated rats of the inbred strains Fischer, Brown Norway, WAG/Rij and Lewis. After intravenous injection of 10, 30 and 50 micrograms copper per 100 gm body weight, two patterns of copper excretion were observed; their profiles varied with the copper dose and the strain of the rats used. The lowest amounts of copper were excreted by Fischer rats, the highest by WAG/Rij rats; this was related to the effect of the copper dose on both patterns. The subcellular distribution of copper in the liver was studied in Fischer and Brown Norway rats after doses of 50, 100, and 200 micrograms per 100 gm body weight. Brown Norway rats accumulated more copper in the liver, although the copper concentration was the same in both strains 1 hr after injection of all doses. Fischer rats accumulated proportionally more copper in lysosomal and nuclear mitochondrial fractions whereas Brown Norway rats accumulated proportionally more copper in the cytosol. Gel filtration of liver supernatants revealed that the amount of copper accumulating in the protein presumed to be metallothionein was 2 to 3 times higher in Brown Norway rats, whereas in the Fischer rats more copper eluted in the void volume fraction. We conclude that both biliary copper excretion and copper distribution in the liver are under genetic control. Because of its low copper excretion and reduced binding of copper to metallothionein the Fischer rat, compared to other strains, may be a suitable model for studying the involvement of the liver in copper intoxication.

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Intracellular distribution of copper in the liver during chronic administration of copper sulfate to the rat

Cited by 35 publications

References 20 publications

Intracellular Distribution of Hepatic Cooper in Normal and Copper-Loaded Sheep

Intracellular Distribution of Hepatic Cooper in Normal and Copper-Loaded Sheep

Pathological mitochondrial copper overload in livers of Wilson's disease patients and related animal models

Strain-related patterns of biliary excretion and hepatic distribution of copper in the rat

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