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There is also some evidence of high manganese and low copper levels in areas of high scrapie incidence [11].
When cells were transferred back from high to low copper levels, there was reappearance of the BiFC fluorescent signal at the plasma membrane.
Other experiments have revealed that only a fraction of hCTR1 is internalized in response to copper, and that hCTR1 internalization is accompanied by its recycling to the plasma membrane when the cells undergo a shift from high to low copper levels [17].
As a necessary pre-translational stage in the process of proving that low copper levels might cause damage to a particular organ, it is necessary to develop an informative animal model.
Samples from the 2 inland districts of Nord-Trøndelag and inner Troms showed high copper concentrations, those from Vesterålen (Sortland) and south-east Norway (Rudshøgda) were intermediate, those from Sogn og Fjordane (Førde) somewhat lower, while samples from Rogaland (Forus) had quite low copper levels.
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Hepatic steatosis has been linked to low liver copper levels in animals receiving low-copper diets [27,28].
It is possible that most Frankia CopA proteins function to provide copper to electron transport chain components, or to maintain low cytoplasmic copper levels during heme synthesis [ 84].
Whether low hepatic copper levels occur in patients with NAFLD or NASH, and could contribute to the pathogenesis of these diseases in animals or patients, remains to be determined.
Reported measurements of hepatic copper in patients with NAFLD or NASH have to date been performed only on dried hepatic tissue that had not been defatted [17], so it remains to be determined whether the reported low hepatic copper levels reflect the actual hepatic copper status in such patients, or rather whether any apparent lowering of hepatic copper is merely factitious.
Severe deficiency can be found by testing for low plasma or serum copper levels, low ceruloplasmin, and low red blood cell superoxide dismutase levels; these are not sensitive to marginal copper status.
At the low end of high dietary copper levels, higher molybdenum levels can help to prevent copper toxicity.
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