LEC rats: An overview of recent findings

Miyoshi, Eiji; Fujii, Junichi; Hayashi, Norio; Taniguchi, Naoyuki

doi:10.1002/(sici)1520-670x(1997)10:2<135::aid-jtra11>3.0.co;2-s

Cited by 13 publications

(4 citation statements)

References 43 publications

(48 reference statements)

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“…The reason for this discrepancy between rat and human seems to be dependent on their etiology. The LEC rat, which was previously investigated, spontaneously develops hereditary hepatitis and hepatoma as the result of an abnormality in copper metabolism, 32 while all patients with HCC enrolled in this study suffered from HCC after a long history of either hepatitis B or C virus infection. In LEC rats, the typical inflammatory cells are relatively few, although many oval cells that are thought to be stem cells for hepatocytes appear in nontumor tissue.…”

Section: Discussionmentioning

confidence: 99%

Gene expression of α1-6 fucosyltransferase in human hepatoma tissues: A possible implication for increased fucosylation of α-fetoprotein

et al. 1998

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The ␣1-6 fucosylated ␣-fetoprotein (AFP) present in serum of patients with hepatocellular carcinoma (HCC) has been employed for the differential clinical diagnosis of HCC from chronic liver diseases. The molecular mechanism by which this alteration occurs, however, remains largely unknown. To address this issue, we purified GDP-L-Fuc:Nacetyl-␤-D-glucosaminide ␣1-6 fucosyltransferase (␣1-6 FucT), an enzyme involved in the ␣1-6 fucosylation of N-glycans from porcine brain, as well as from a human gastric cancer cell line, and cloned their genes. In this study, levels of ␣1-6 FucT mRNA expression and the activity of this enzyme for 12 human HCC tissues were examined and compared with that in surrounding tissues and normal livers. The mean ؎ SD for ␣1-6 FucT activity was 78 ؎ 41 pmol/h/mg in normal control liver, 202 ؎ 127 pmol/h/mg in adjacent uninvolved liver tissues (chronic hepatitis: 181 ؎ 106 pmol/h/mg; liver cirrhosis: 233 ؎ 164 pmol/h/mg), and 195 ؎ 72 pmol/h/mg in HCC tissues. The mRNA expression of ␣1-6 FucT was also enhanced in proportion to enzymatic activity except for a few cases, suggesting that ␣1-6 FucT expression is increased in chronic liver diseases, especially liver cirrhosis. Transfection of ␣1-6 FucT gene into cultured rat hepatocytes markedly increased ␣1-6 FucT activity and led to an increase in lens culinaris agglutinin (LCA) binding proteins in both cell lysates and condition media. When the ␣1-6 FucT gene was transfected into a human HCC cell line, Hep3B, which originally showed low levels of ␣1-6 FucT expression, ␣1-6-fucosylated AFP was dramatically increased in the condition media. Collectively, these results suggest that the enhancement of ␣1-6 FucT expression increased the fucosylation of several proteins, including AFP, and that the level of ␣1-6-fucosylated AFP in patients with HCC was in part caused by up-regulation of the ␣1-6 FucT gene expression. (HEPATOLOGY 1998;28:944-952.)

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Section: Discussionmentioning

confidence: 99%

Gene expression of α1-6 fucosyltransferase in human hepatoma tissues: A possible implication for increased fucosylation of α-fetoprotein

et al. 1998

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“…Although the exact onset of the disease varies, depending on the report, LEC rats spontaneously develop acute hepatitis at 12 to 24 weeks after birth, followed by chronic hepatitis (Miyoshi et al, 1997a). At 40 weeks of age, they begin to develop nodules in the liver which progress to hepatoma.…”

Section: Wiley-liss Incmentioning

confidence: 99%

High expression of α‐1‐6 fucosyltransferase during rat hepatocarcinogenesis

et al. 1998

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␣-1-6 Fucosylated ␣-fetoprotein (AFP) is known to be elevated in patients with primary hepatoma and has been suggested as being useful as an early indicator and predictor of the poor prognosis for hepatoma. Although GDP-L-fucosyl-N-acetyl-␤-D-glucosaminide ␣-1-6 fucosyltransferase (␣-1-6 FucT), is the key enzyme involved in ␣-1-6 fucosylation of AFP, when and how the expression of ␣-1-6 FucT is enhanced during hepatocarcinogenesis is unknown. Recently, we established a convenient assay method for this enzyme and were successful in the purification and cDNA cloning of ␣-1-6 FucT from human gastric cancer, as well as from porcine brain. In the present study, levels of ␣-1-6 FucT activity and mRNA expression have been determined during hepatocarcinogenesis in LEC rats which spontaneously develop hereditary hepatitis and hepatoma. The fetal liver contained the highest enzymatic activity, which tended to increase in inverse proportion to gestation. The enzymatic activity was significantly increased in hepatoma tissues as compared with uninvolved adjacent tissues. Northern-blot analysis revealed high expression of ␣-1-6 FucT mRNA in hepatoma tissues, whereas the expression was fairly low in normal, hepatitis and uninvolved adjacent liver tissues. While the fetal liver had the highest enzymatic activity, the expression of ␣-1-6 FucT mRNA was low, suggesting that another ␣-1-6 FucT is induced in fetal liver or that post-translational modification occurs. High expression of ␣-1-6 FucT was also observed in 3Ј-MeDABinduced rat hepatomas and some rat hepatoma cell lines. Collectively, ␣-1-6 FucT was strongly enhanced from an early stage of hepatocarcinogenesis and was maintained at a high level in rat hepatomas. Int.

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“…The Long-Evans rats with a cinnamon-like coat colour (LEC rat) have already been identified as an excellent animal model for studying Wilson's disease (WD; Miyoshi et al 1997). These rats have a mutation in Atp7b that encodes P-type adenosine triphosphatase, a gene homologous to the WD gene (Wu et al 1994) and show some of the clinical features of the disease including hepatic copper (Cu) accumulation and reduced biliary Cu excretion.…”

Section: Introductionmentioning

confidence: 99%

Metallothionein-1 and metallothionein-2 gene expression and localisation of apoptotic cells in Zn-treated LEC rat liver

Santon

Sturniolo

Albergoni

et al. 2003

Histochem Cell Biol

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The aims of the present work were to determine the effect of long-term treatment with zinc (Zn) on metallothionein (MT) concentrations and to study the levels of both MT-1 and MT-2 mRNAs in Long-Evans Cinnamon (LEC) rat liver. We also identified apoptotic cells comparing two cytochemical techniques. Thirteen rats received 50 mg zinc acetate daily by gavage, 13 rats received no treatment, and both groups were killed after 60 days. Finally four rats were killed 35 days after birth (T 0 ). The results demonstrate that the Zn-treated group had higher levels of MT than both the untreated and basal ones. Quantification of mRNA indicates that the level of the Zn-treated group was significantly higher than the untreated group. Confocal fluorescent staining with monoclonal antibody (Mab) against single-strand DNA localised the hepatic cells that had chromatin condensation and nuclear fragmentation typical of apoptosis, especially in the untreated group sections. The intensity and quantity of fluorescence decreased in both the treated and basal groups. The higher sensitivity of Mab staining compared to TUNEL, which revealed both apoptotic and necrotic cells, reflects the different action mechanism of the two techniques. These findings confirm, in LEC rats, the important role of Zn in cellular protection in relation to MT expression and apoptotic processes as cellular responses to DNA damage by free radicals.

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LEC rats: An overview of recent findings

Cited by 13 publications

References 43 publications

Gene expression of α1-6 fucosyltransferase in human hepatoma tissues: A possible implication for increased fucosylation of α-fetoprotein

Gene expression of α1-6 fucosyltransferase in human hepatoma tissues: A possible implication for increased fucosylation of α-fetoprotein

High expression of α‐1‐6 fucosyltransferase during rat hepatocarcinogenesis

Metallothionein-1 and metallothionein-2 gene expression and localisation of apoptotic cells in Zn-treated LEC rat liver

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