| Effects of Mercuric Chloride on Gene Expression in NRK-52E Cells. |
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Joon Ik Ahn, Si Yeon Baik, Moon Jeong Ko, Hee Jung Shin, Hye Joo Chung, Ho Sang Jeong |
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Pharmacological Research Division, Toxicological Evaluation Research Department, National Institute of Food and Drug Safety Evaluation, Seoul 122-704, Korea. hosa33@korea.kr |
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| Abstract |
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Mercuric chloride, a model nephrotoxicant was used to elucidate time- and dose-dependent global gene expression changes associated with proximal tubular toxicity. Rat kidney cell lines NRK-52E cells were exposed for 2, 6 and 12 hours and with 3 different doses of mercuric chloride. Cell viability assay showed that mercuric chloride had toxic effects on NRK-52E cells causing 20% cell death (IC20) at 40micrometer concentration. We set this IC20 as high dose concentration and 1/5 and 1/25 concentration of LC20 were used as mid and low concentration, respectively. Analyses of microarray data revealed that 738 genes were differentially expressed (more than two-fold change and p<0.05) by low concentration of mercuric chloride at least one time point in NRK-52E cells. 317 and 2,499 genes were differentially expressed at mid and high concentration of mercuric chloride, respectively. These deregulated genes showed a primary involvement with protein trafficking (CAV2, CANX, CORO1B), detoxification (GSTs) and immunity and defense (HMOX1, NQO1). Several of these genes were previously reported to be up-regulated in proximal tubule cells treated with nephrotoxicants and might be aid in promoting the predictive biomarkers for nephrotoxicity. |
| Keywords:
gene expression; mercuric chloride; nephrotoxicity; NRK-52E cells |
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