scholarly journals Glutathione-doxorubicin conjugate expresses potent cytotoxicity by suppression of glutathione S-transferase activity: comparison between doxorubicin-sensitive and -resistant rat hepatoma cells

1997 ◽  
Vol 76 (10) ◽  
pp. 1333-1337 ◽  
Author(s):  
T Asakura ◽  
K Ohkawa ◽  
N Takahashi ◽  
K Takada ◽  
T Inoue ◽  
...  
Keyword(s):  
Hepatoma Cells ◽  
Transferase Activity ◽  
Glutathione S Transferase ◽  
Activity Comparison ◽  
Rat Hepatoma ◽  
Rat Hepatoma Cells

scholarly journals METABOLISM OF BILIRUBIN BY A CLONAL STRAIN OF RAT HEPATOMA CELLS

1970 ◽  
Vol 47 (3) ◽  
pp. 703-710 ◽  
Author(s):  
Hans E. Rugstad ◽  
Stephen H. Robinson ◽  
Claudine Yannoni ◽  
Armen H. Tashjian
Keyword(s):  
Average Rate ◽  
Hepatoma Cells ◽  
Cell Protein ◽  
Bile Pigment ◽  
Transferase Activity ◽  
Glucuronyl Transferase ◽  
Clonal Strain ◽  
Bilirubin Metabolism ◽  
Rat Hepatoma ◽  
Rat Hepatoma Cells

These studies demonstrate that the MH1C1 strain of rat hepatoma cells has the ability to take up and conjugate bilirubin and then excrete the conjugated pigment into the culture medium. On incubation with unconjugated bilirubin, the average rate of appearance of conjugated bilirubin in the medium was 4.4 ± 0.20 µg per mg of cell protein per hour (mean ± SE). The products formed from bilirubin by MH1C1 cells were chromatographically identical to those found in normal rat bile. Assay of bilirubin UDP glucuronyl transferase activity in homogenates of MH1C1 cells gave a value of 3.3 ± 0.50 µg of conjugated pigment formed per mg protein per hour, only moderately less than the enzyme activity of liver from normal rats. Rat fibroblasts in culture did not conjugate bilirubin, nor did they contain bilirubin UDP-glucuronyl transferase activity. As in living animals, flavaspidic acid inhibited bilirubin metabolism by MH1C1 cells, suggesting that the mechanism for bilirubin uptake is similar to that of normal liver. In contrast to the findings in animals, however, preincubation of MH1C1 cells with phenobarbital led to only minimal enhancement of pigment conjugation. MH1C1 cells represent the first example of a clonal strain of cells in culture in which many of the pathways of hepatic bilirubin metabolism remain intact. They should, therefore, serve as a useful model for studies of bile pigment metabolism which are not easily performed in the living animal.

scholarly journals Transcription factor Nrf2/MafK regulates rat placental glutathione S-transferase gene during hepatocarcinogenesis

2004 ◽  
Vol 380 (2) ◽  
pp. 515-521 ◽  
Author(s):  
Hiromi IKEDA ◽  
Shinzo NISHI ◽  
Masaharu SAKAI
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Transcription Factor ◽  
Phase Ii ◽  
Hepatoma Cells ◽  
Carcinoma Cells ◽  
Glutathione S Transferase ◽  
P Gene ◽  
Rat Hepatoma ◽  
Rat Hepatoma Cells

The rat GST-P (placental glutathione S-transferase), a phase II detoxifying enzyme, is not expressed in normal liver cells, but is highly and specifically induced during early hepatocarcinogenesis as well as in hepatocellular carcinoma cells. Results of previous studies indicated that GST-P gene activation was mainly controlled by an enhancer element, GPE1 (GST-P enhancer 1), but the specific activation mechanism of the GST-P gene was not fully understood [Morimura, Suzuki, Hochi, Yuki, Nomura, Kitagawa, Nagatsu, Imagawa and Muramatsu (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 2065–2068; Suzuki, Imagawa, Hirabayashi, Yuki, Hisatake, Nomura, Kitagawa and Muramatsu (1995) Cancer Res. 55, 2651–2655]. In the present study, we investigate the transcription factor Nrf2/MafK heterodimer (where Nrf2 stands for NF-E2 p45-related factor 2) as an activator of the GST-P gene through the action of GPE1 during hepatocarcinogenesis. Electrophoretic mobility-shift assay and footprinting analysis with wild-type GPE1 and GPE1 point mutants showed that the Nrf2/MafK heterodimer specifically bound GPE1. Reporter transfection assays indicated that Nrf2 strongly stimulated GST-P gene expression in mouse F9 embryonal carcinoma cells and H4IIE rat hepatoma cells. Northern-blot analysis indicated that GST-P and Nrf2 mRNA increased in parallel with development of precancerous lesions and hepatocellular carcinoma. Keap1 (Kelch-like ECH-associated protein 1), an inhibitory factor of Nrf2, decreased the activation of GPE1 by Nrf2 and this suppression was restored after treatment with electrophilic compounds. GST-P mRNA expression in H4IIE cells was induced by electrophilic compounds, as was the expression of mRNAs of other phase II detoxifying enzymes. Chromatin immunoprecipitation analyses showed that antibodies both against Nrf2 and against MafK precipitated GPE1 from the chromatin of the pre-neoplastic hepatocytes and rat hepatoma cells (H4IIE and dRLh84), but not from normal hepatocytes. These results indicate that the Nrf2/MafK heterodimer regulates GST-P gene expression during early hepatocarcinogenesis and in hepatoma cells.

scholarly journals Identification of the insulin receptor tyrosine residues undergoing insulin-stimulated phosphorylation in intact rat hepatoma cells.

1988 ◽  
Vol 263 (1) ◽  
pp. 350-359 ◽  
Author(s):  
H E Tornqvist ◽  
J R Gunsalus ◽  
R A Nemenoff ◽  
A R Frackelton ◽  
M W Pierce ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Hepatoma Cells ◽  
Tyrosine Residues ◽  
Rat Hepatoma ◽  
Rat Hepatoma Cells
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