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.
Animals ; Cell Death ; Cell Line ; Cell Survival ; Gene Expression ; Kidney ; Mercuric Chloride ; Protein Transport ; Rats ; Biomarkers

BACKGROUND AND OBJECTIVES: Mucin gene expression and mucin production are highly increased during inflammatory airway disorders such as, asthma, chronic bronchitis and sinusitis. Cytokines, lipopolysaccharides and other inflammatory mediators are related with secretion and production of mucin. However, among of inflammatory mediators, the relation of leukotrienes and mucin genes expression is not clear. The aim of this study is to evaluate MUC2/5AC genes expression and mucin secretion through leukotriene receptor in human airway epithelial cells. SUBJECTS AND METHOD: The effect of Leukotriene D4 and leukotriene receptor antagonist, pranlukast hydrate (ONO-1078) on the regulation of MUC2/5AC gene expression and mucin secretion was observed in the human airway NCI-H292 epithelial cells. The mRNA levels of MUC2/5AC and the amount of mucin protein were determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunoassay. RESULTS: Leukotriene D4 upregulated MUC2/5AC gene expression and mucin secretion on a dose dependent pattern. Pranlukast hydrate (ONO-1078, 100 micrometer) downregulated the leukotriene D4-mediated MUC2/5AC gene expression and mucin secretion. CONCLUSION: These results suggest that the leukotriene receptor system is one of the expression mechanisms of MUC2/5AC genes and mucin secretion.
Asthma ; Bronchitis, Chronic ; Cytokines ; Epithelial Cells* ; Gene Expression ; Humans* ; Immunoassay ; Leukotriene Antagonists ; Leukotriene D4 ; Leukotrienes ; Lipopolysaccharides ; Mucins* ; Receptors, Leukotriene* ; RNA, Messenger ; Sinusitis

No abstract available.
Antiviral Agents/therapeutic use ; Ascites/diagnosis/prevention & control/therapy ; Cholagogues and Choleretics/therapeutic use ; Fatty Liver/diagnosis/diet therapy ; Fatty Liver, Alcoholic/diagnosis/drug therapy ; Hemorrhage/prevention & control/therapy ; Hepatic Encephalopathy/diagnosis/prevention & control/therapy ; Hepatitis B, Chronic/diagnosis/drug therapy ; Hepatitis C, Chronic/diagnosis/drug therapy ; Humans ; Liver Cirrhosis/*diagnosis/drug therapy/pathology/*therapy ; Liver Cirrhosis, Biliary/drug therapy ; Vasodilator Agents/therapeutic use