• Title/Summary/Keyword: WB-F344 rat liver epithelial cells

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Gene Expression Analysis of Methotrexate-induced Hepatotoxicity between in vitro and in vivo

  • Jung, Jin-Wook;Kim, Seung-Jun;Kim, Jun-Sup;Park, Joon-Suk;Yeom, Hye-Jung;Kim, Ji-Hoon;Her, Young-Sun;Lee, Yong-Soon;Kang, Jong-Soo;Lee, Gyoung-Jae;Kim, Yang-Seok;Kang, Kyung-Sun;Hwang, Seung-Yong
    • Molecular & Cellular Toxicology
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    • v.1 no.4
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    • pp.256-261
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    • 2005
  • The recent DNA microarray technology enables us to understand gene expression profiling in cell line and animal models. The technology has potential possibility to comprehend mechanism of multiple genes were related to compounds which have toxicity in biological system. So, microarray system has been used for the prediction of toxicity through gene expression induced by toxicants. It has been shown that compounds with similar toxic mechanisms produce similar changes in gene expression in vivo system. Here we focus on the use of toxicogenomics for the determination of gene expression analysis associated with hepatotoxicity in rat liver and cell line (WB-F344). Methotrexate (MTX) is a chemotherapy agent that has been used for many years in the treatment of cancer because it affects cells that are rapidly dividing. Also it has been known the toxicity of MTX, in a MTX abortion, it stops embryonic cells from dividing and multiplying and is a non-surgical method of ending pregnancy in its early stages. We have shown DNA microarray analyses to assess MTX-specific expression profiles in vivo and in vitro. Male Sprague-Dawely VAF+ albino rats of 5-6 weeks old and WB-F344 cell line have been treated with MTX. Total RNA was isolated from Rat liver and cell line that has treated with MTX. 4.8 K cDNA microarray in house has been used for gene expression profiling of MTX treatment. We have found quite distinct gene expression patterns induced by MTX in a cell line and in vivo system.

Inhibition of Gap Junctional Intercellular Communication by Food Preservatives Potassium Sorbate (소르빈산 칼륨의 GJIC 억제로 인한 간독성 유발)

  • Hwang, Jae-Woong;Chung, Ji-Hye;Jung, Ji-Won;Jung, Ji-Youn;Kim, Sun-Jung;Park, Jung-Ran;Ahn, Ji-Yun;Ha, Tae-Youl;Kim, Sung-Ran;Lee, Yong-Soon;Kang, Kyung-Sun
    • Journal of Food Hygiene and Safety
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    • v.21 no.4
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    • pp.269-273
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    • 2006
  • Potassium Sorbate (PS) is a potassium salt version of sorbic acid, which has antimicrobial and fungistatic features in foods. Therefore, PS is used as a food preservative against fungi and mold. PS has been found to be non-toxic even when taken in large quantities given its trait to be broken down in the body into water and carbon dioxide. Gap Junctional Intercellular Communication (GJIC) is essential in the maintenance of tissue homeostasis during development and differentiation. This study was made of the effects of PS on GJIC in WB-F344 rat liver epithelial (WB) cells. We found dramatic decrease of cell viability in time- and dose-dependent manners when WB cells were treated with PS. The effect of PS on GJIC is strong inhibition, and it took place in parallel with a hyperphosphorylation of connexin 43 expression. The finding that PS interferes with gap junction functionality should be considered with respect to the mechanism of PS-induced hepatotoxicity.

GAP JUNCTION, A BIOMARKER FOR CANCER AND CHEMOPREVENTION: PREVENTIVE EFFECT OF EPICATECHIN AND GINSENOSIDE $Rb_$ ON THE INHIBITION OF GAP JUNCTIONAL INTERCULLULAR COMMUNICATION BY TPA AND $H_2O_2$

  • Kang, Kyung-Sun;Lee, Yong-Soom
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05b
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    • pp.59-72
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    • 2002
  • The anticarcinogenic effects of epicatechin(EC) and ginsenoside Rb2(Rb2), which are major components of green tea and Korea ginsen, respectively, were investigated using a model system of gap junctional intercellular communication (GJIC) in WB-F344 rat liver epithelial cells. 12-O-Tetradecanoylphorbol-13-accetate (TPA) and hydrogen preoxide, known as cancer promoters, inhibited GJIC in the epithelial cells as determined by the scrape loading/dye transfer assay, fluorescence redistribution assay after photobleaching, and immunofluorescent staining of connexin 43 using a laser confocal microscope. The inhibition of GJIC by TPA and H2O2 was prevented with treatment of Rb2 or Ec. The effect of EC on GJIC was stronger in TPA-treated cells than in H2O2-treated cells, while the effect of Rb2 was opoosite to that of EC. EC, at the concentration of 27.8$\mu$g/ml, prevented the TPA-induced GJIC inhibition by about 60%. Rb2, at the concentration of 277$\mu$g/ml, recovered the H2O2-induced GJIC inhibition by about 60%. These results suggest that Rb2 and EC may prevent human cancers by preventing the down-regulation of GJIC during the cancer promotion phase and that the anticancer effect of green tea and Korea ginseng may come from the major respective conponents, EC and Rb2.

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PREVENTIVE EFFECT OF MUSHROOM PHELLINUS LINTEUS ON THE INHIBITION OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION BY $H_2O_2$ IS INVOLVED IN THE UP-REGULATION OF ERK2 AND p38

  • Kang, Kyung-Sun;Cho, Jong-Ho;Cho, Sung-Dae;Kim, Kyung-Bae;Lee, Ji-Hae;Ahn, Nam-Shik;Jung, Ji-Won;Yang, Se-Ran;Park, Joon-Suk;Yoon, Byung-Su;Kim, Sung-Hoon;Lee, Yong-Soon
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.159-160
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    • 2001
  • Gap junctional intercellular communication (GJIC) is a cellular event underlying the tumor promotion process and that treatment to prevent the down-regulation or to up-regulate GJIC is important in preventing tumor promotion. We evaluated the potential preventive effect of Mushroom Phellinus Linteus (PL) against the promoting action of hydrogen peroxide ($H_2O$$_2$) in WB-F344 rat liver epithelial cells.(omitted)

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Antioxidative Activity of Cherry Tomato (Lycopersicon lycopersicum var. cerasiforme) Extracts and Protective Effect for $H_2O_2$-induced Inhibition of Gap Junction Intercellular Communication

  • Kim, Su-Na;Choi, Won-Hee;Ahn, Ji-Yun;Ha, Tae-Youl
    • Food Science and Biotechnology
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    • v.18 no.3
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    • pp.630-635
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    • 2009
  • This study was performed to analyze various antioxidants, to evaluate the antioxidative activities, and to measure the protective effect for gap junction intercellular communication (GJIC) to assess the functional potency of the cherry tomato. The ascorbic acid, lycopene, and ${\beta}-carotene$ were measured at $503.4{\pm}9.6$, $39.7{\pm}1.5$, and $7.4{\pm}0.3$ mg/100 g d.w., and ${\alpha}-$, ${\beta}+{\gamma}-$, ${\delta}-tocopherol$ contents were measured at $8.3{\pm}0.1$, $1.7{\pm}0.0$, and $0.1{\pm}0.0$ mg/100 g d.w., respectively. Cherry tomato extract using hexane/acetone/EtOH (2:1:1, CTE) exhibited a ABTS radical scavenging activity with an $IC_{50}$ value of $48.83{\pm}0.30\;{\mu}g/mL$. The cherry tomato protected against the inhibition of GJIC induced by $H_2O_2$ in WB-F344 rat liver epithelial cells, and the reduction in phosphorylated Cx43 was most clearly correlated with the concentration of CTE. These results demonstrated that the cherry tomato harbors a wealth of potent antioxidants and might be protect human body against the inhibition of the GJIC by toxic components.

Effect of 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose isolated from Galla Rhois on gap junctional intercellular communication and antiangiogenic activity (오배자 BuOH층에서 분리한 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose의 세포간교통 회복 및 혁관형성 억제작용에 대한 효과)

  • Huh Jeong Eun;Lee Hyo Jung;Song Gyu Yong;Cha Bae Cheon;Kim Han Sung;Yoo Dong Youl;Ryu Shi Yong;Kim Sung Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.16 no.3
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    • pp.452-457
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    • 2002
  • Galla Rhois is a gallnut of Rhus javanica Linne used for treatment of diarrhea, hemorrhage, cough, leukorrhea and toxic tumor etc in oriental medicine. For the evaluation of antitumor effect of Galla Rhois, activity based fractionation was done. We isolated an effective compound and identified 1,2,3,4,6-penta-O-galloyl-β-D-glucose(PGG) by photometric analysis such as NMR and MASS. Then, we studied the angiogenic activity of PGG. It showed a cytotoxicity against SK-OV-3, SK-OV-3, HT1080 with IC/sub 50/ of 50 ug/ml approximately. It also effectively inhibited proliferation of HUVEC cells treated by bFGF to 30% of control at 20 ug/ml and cell migration to 80% at 10 ug in a dose dependent fashion. Tube formation of HUVEC cells on matrigel was effectively suppressed from 2.5 ug/ml of concentration by PGG. Moreover, it effectively recovered the dysfunction of gap junctional intercellular communication in WB-F344 rat liver epithelial cells caused by hydrogen peroxide at 4 ug/ml suggesting it potently can inhibit tumor promotion. Taken together, it indicates 1,2,3,4,6-penta-O-galloyl- β -D-glucose has antiangiogenic activity.