Fe(II)/Cu(I)-dependent P-type ATPase activity in the liver of long-evans cinnamon rats

Takeda, Kazuo; Eguchi, Hiroshi; Soeda, Shiori; Shirahata, Akira; Kawamura, Masaru

doi:10.1016/j.lfs.2004.10.041

Cited by 4 publications

(3 citation statements)

References 16 publications

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“…Different studies have described that liver of Long-Evans Cinnamon (LEC) rat (animal model of human Wilson's disease), which exhibits abnormal hepatic copper and iron concentration due to the deletion of the p-type copper transport ATPase gene (Atp7b), possesses a feature of increase in polyploidy (enlarged hepatocytes with huge nuclei) and a delay in mitotic progression. Interestingly, injection of irondextran in normal mice induces liver polyploidization; this effect is inhibited by the oral intake of iron chelator [60, 61]. …”

Section: Hepatocytes Polyploidy and Liver Growthmentioning

confidence: 99%

Hepatocytes Polyploidization and Cell Cycle Control in Liver Physiopathology

Gentric

Desdouets

Celton-Morizur

2012

International Journal of Hepatology

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Most cells in mammalian tissues usually contain a diploid complement of chromosomes. However, numerous studies have demonstrated a major role of “diploid-polyploid conversion” during physiopathological processes in several tissues. In the liver parenchyma, progressive polyploidization of hepatocytes takes place during postnatal growth. Indeed, at the suckling-weaning transition, cytokinesis failure events induce the genesis of binucleated tetraploid liver cells. Insulin signalling, through regulation of the PI3K/Akt signalling pathway, is essential in the establishment of liver tetraploidization by controlling cytoskeletal organisation and consequently mitosis progression. Liver cell polyploidy is generally considered to indicate terminal differentiation and senescence, and both lead to a progressive loss of cell pluripotency associated to a markedly decreased replication capacity. Although adult liver is a quiescent organ, it retains a capacity to proliferate and to modulate its ploidy in response to various stimuli or aggression (partial hepatectomy, metabolic overload (i.e., high copper and iron hepatic levels), oxidative stress, toxic insult, and chronic hepatitis etc.). Here we review the mechanisms and functional consequences of hepatocytes polyploidization during normal and pathological liver growth.

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Section: Hepatocytes Polyploidy and Liver Growthmentioning

confidence: 99%

Hepatocytes Polyploidization and Cell Cycle Control in Liver Physiopathology

Gentric

Desdouets

Celton-Morizur

2012

International Journal of Hepatology

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“…9 The atp7b or Wilson's disease protein is a Cu-transporting P-type ATPase responsible not only for Cu loading into the trans-Golgi network but also for biliary Cu efflux. 10 Wu et al 11 identified the LEC Atp7b gene mutation. The disease causing mutation is a deletion of 900 bp in the 3′-terminus which removes the critical ATP binding domain of the wild-type gene leading to a non-functional protein.…”

Section: Copper Accumulation In Lec Ratsmentioning

confidence: 99%

The LEC rat: a useful model for studying liver carcinogenesis related to oxidative stress and inflammation

Márquez

Villa‐Treviño

Guéraud³

2007

Redox Report

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Growing evidence indicates oxidative stress as a mechanism of several diseases including cancer. Oxidative stress can be defined as the imbalance between cellular oxidant species production and antioxidant capability shifted towards the former. Lipid peroxidation is one of the processes that takes place during oxidative stress. Lipid peroxidation products, such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE), are closely related to carcinogenesis as they are potent mutagens and they have been suggested as modulators of signal pathways related to proliferation and apoptosis, two processes implicated in cancer development. Mechanisms by which oxidative stress leads to tumor formation are still under investigation. The need of suitable in vivo models that could reflect that inflammation-related human carcinogenesis is evident. In this regard, the mutant strain Long Evans Cinnamon-like (LEC) rat provides a promising model for investigation of the relationship between hepatitis induced by oxidative stress and hepatocarcinogenesis because it has been demonstrated to develop spontaneous liver tumor formation related to copper accumulation and oxidative stress. In this review, the findings regarding oxidative stress and its relation with liver pathologies in LEC rats are discussed; we focus on the mechanisms proposed for HNE carcinogenesis.

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“…In these circumstances, the liver polyploidy profile can also be modified. Signals promoting hepatocyte polyploidy include liver regeneration following partial hepatectomy (14), metabolic overload (15,16), chemical overload (17), oxidative damage (18), and viral infection (5). However, the cellular and molecular mechanisms regulating polyploidy in these different situations are not fully understood.…”

Section: Introductionmentioning

confidence: 99%