Histochemical demonstration of copper in LEC rat liver

Fujii, Yukiko; Shimizu, K; Satoh, M.; Fujita, Miri; Fujioka, Yasunori; Li, Y.; Togashi, Yuji; Takeichi, Noritoshi; Nagashima, Kazuo

doi:10.1007/bf00270043

Cited by 21 publications

(10 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Strikingly, maximum copper levels were reached before the onset of hepatitis. Thereafter, copper levels increased only in the particulate fraction of the liver, which is consistent with the findings of others [ 19–23]. An accumulation of copper in the particulate fraction of the liver has also been reported in symptomatic Wilson's disease patients [ 24].…”

Section: Discussionsupporting

confidence: 91%

Association of copper to metallothionein in hepatic lysosomes of Long–Evans cinnamon (LEC) rats during the development of hepatitis

Klein¹,

Lichtmannegger

Heinzmann

et al. 1998

Eur J Clin Investigation

View full text Add to dashboard Cite

We suggest that chronic copper toxicity in LEC rats involves the uptake of copper-loaded MT into lysosomes, where it is incompletely degraded and polymerizes to an insoluble material containing reactive copper. This copper, together with iron, initiates lysosomal lipid peroxidation, leading to hepatocyte necrosis. Subsequent to phagocytosis by Kupffer cells, the reactive copper may amplify liver damage either directly or through stimulation of these cells.

show abstract

Section: Discussionsupporting

confidence: 91%

Association of copper to metallothionein in hepatic lysosomes of Long–Evans cinnamon (LEC) rats during the development of hepatitis

Klein¹,

Lichtmannegger

Heinzmann

et al. 1998

Eur J Clin Investigation

View full text Add to dashboard Cite

show abstract

“…The Long-Evans rat with a cinnamon-like coat color (LEC) is a mutant animal in which agedependent Cu accumulates in the liver and kidneys, resulting in damage to the organs. These rats have been used as model animals to study Cu metabolic disorders (5)(6)(7)(8). Metallothionein (MT) is as-sociated with Cu metabolic disorders, since age-dependent accumulation of Cu binding MT (Cu-MT) was shown to occur in LEC rats (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Direct visualization of copper-metallothionein in LEC rat kidneys: application of autofluorescence signal of copper-thiolate cluster.

Okabe¹,

Nakayama²,

Kurasaki³

et al. 1996

J Histochem Cytochem.

View full text Add to dashboard Cite

We report on the histochemistry of copper-metallothioneh (Cu-MT) in the kidneys ofLong Evans Cinnamon (LEC) rats. We used the visualization principle of histochemistry based on the autofluorescence emission from the fluorophore of Cu + -thiolate clusters in proteins. Intense autofluorescenm signals were observed with a ring at the outer stripe of the outer medulla. Orange fluorescence signals were observed in the nudei and cytoplasm of pnaunal Saaight tubular (PST) cells of segment 3 (S3) at the outex Smpe ofthe outer medulla, and yellow-orange signals were detected in lysosome-like organelles in the proximal convoluted tubule (PCT) cells of segments 1 and 2 (SI and S2) adjacent to the glomeruli in the cortex. These fluomcent materials were identified as Cu-MT because both signals were quenched by withdrawing Cu + or by blocking cysteine residues, the distributions of cysteine residues and immunoreactive MT showed identical

show abstract

“…Copper chelation, fundamental treatment for the disease, further reduces hypo‐CP‐emia, and induces the replacement of copper by iron in the hepatocellular lysosomes of male patients . These observations are compatible with the double overloads of copper and iron in Long‐Evans Cinnamon (LEC) rats with hypo‐CP‐emia and a large deletion in atp7b , and related to the iron disease of ACP patients . Low iron saturation of the circulating transferrin in the classical WD may suppress hepcidin25 synthesis via TFR2 as ACP, and result in iron accumulation in the liver.…”

Section: Liver Structures Of Patients With Iron Overload Syndromes Anmentioning

confidence: 59%

The interactions between iron and copper in genetic iron overload syndromes and primary copper toxicoses in Japan

Tatsumi

Kato

et al. 2018

Hepatology Research

View full text Add to dashboard Cite

Iron and copper are trace elements essential for health, and iron metabolism is tightly regulated by cuproproteins. Clarification of the interactions between iron and copper may provide a better understanding of the pathophysiology and treatment strategy for hemochromatosis, Wilson disease, and related disorders. The hepcidin/ferroportin system was used to classify genetic iron overload syndromes in Japan, and ceruloplasmin and ATP7B were introduced for subtyping Wilson disease into the severe hepatic and classical forms. Interactions between iron and copper were reviewed in these genetic diseases. Iron overload syndromes were classified into pre-hepatic iron loading anemia and aceruloplasminemia, hepatic hemochromatosis, and post-hepatic ferroportin disease. The ATP7B-classical form with hypoceruloplasminemia has primary hepatopathy and late extra-hepatic complications, while the severe hepatic form is free from ATP7B mutation and hypoceruloplasminemia, and silently progresses to liver failure. A large amount of iron and trace copper co-exist in hepatocellular dense bodies of all iron overload syndromes. Cuproprotein induction to stabilize excess iron should be differentiated from copper retention in Wilson disease. The classical form of Wilson disease associated with suppressed hepacidin25 secretion may be double-loaded with copper and iron, and transformed to an iron disease after long-term copper chelation. Iron disease may not be complicated with the severe hepatic form with normal ferroxidase activity. Hepatocellular dense bodies of iron overload syndromes may be loaded with a large amount of iron and trace copper, while the classical Wilson disease may be double-loaded with copper and iron.

show abstract

Histochemical demonstration of copper in LEC rat liver

Cited by 21 publications

References 14 publications

Association of copper to metallothionein in hepatic lysosomes of Long–Evans cinnamon (LEC) rats during the development of hepatitis

Association of copper to metallothionein in hepatic lysosomes of Long–Evans cinnamon (LEC) rats during the development of hepatitis

Direct visualization of copper-metallothionein in LEC rat kidneys: application of autofluorescence signal of copper-thiolate cluster.

The interactions between iron and copper in genetic iron overload syndromes and primary copper toxicoses in Japan

Contact Info

Product

Resources

About