Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1522282 (EMT)
 2,868 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-dodecylimidazole is a compound which acquires detergent properties under acidic conditions and might be useful in killing selectively cells in those regions of solid tumours which have a reduced extracellular pH (pHe). We have therefore studied the effects of N-dodecylimidazole against malignant cells in tissue culture. N-dodecylimidazole displayed pHe-dependent cytotoxicity against EMT-6 and MGH U1 cells; cell killing was dose dependent and was 100-fold greater at pHe 6.0 than pHe 7.0. Reduced toxicity of N-dodecylimidazole was observed at higher cell concentrations (> 10(6) cells ml-1), and only minor effects were observed against multicellular tumour spheroids. Potential mechanisms of action of N-dodecylimidazole include detergent-mediated lysis of the cell membrane at low pHe, and selective uptake into lysosomes where detergent activity leads to rupture of the lysosomal membrane and release of cytolytic enzymes. Inhibition of activity of cysteine proteases by the inhibitor E-64 did not protect cells against the toxicity of N-dodecylimidazole, suggesting that these lysosomal enzymes do not play a major role in the mechanism of action of this compound. Lysis of erythrocytes (which contain no lysosomes) was observed with low concentrations of N-dodecylimidazole. Dependence of cell lysis on cell concentration was similar to that observed for two other detergents that act on the plasma membrane, Triton X-100 and sodium dodecyl sulfate. We conclude that N-dodecylimidazole causes pHe dependent cell killing in two cultured tumour cell lines, and that its mechanism of action is probably due to acid mediated production of detergent activity which acts primarily on the cell plasma membrane.
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PMID:pH dependent cytotoxicity of N-dodecylimidazole: a compound that acquires detergent properties under acidic conditions. 842 83

The non-neuronal monoamine transporters OCT1, OCT2 and EMT (human gene symbols SLC22A1-A3) efficiently transport a number of positively-charged monoamines and some small organic cations across the plasma membrane, and thus are implicated in the inactivation of released monoamine transmitters (e.g. noradrenaline, histamine, agmatine) in vivo. Although prostaglandins are full anions at physiological pH, data from a recent publication suggest efficient transport of the prostaglandins PGE2 and PGF2alpha by OCT1 and OCT2. In the present study we have reexamined transport of PGE2 by OCT2 from human (OCT2h). Uptake of substrate into monolayers of 293 cells, stably transfected to express OCT2h, was compared to uptake into non-transfected control cells. Efficiency of transport of the established substrate 3H-1-methyl-4-phenylpyridinium (MPP+), expressed as clearance, was high at 81 microl min(-1) mg protein(-1) on average. By contrast, uptake of 3H-PGE2 was virtually identical for control cells and OCT2h cells. The efficiency of transport was 0.1+/-0.6, 1.0+/-0.3, and 0.7+/-0.4 microl min(-1) mg protein(-1) for cell lysis with methanol, HClO4, and Triton X-100 respectively. Similar results were obtained with unlabeled MPP+ (192+/-12 microl min(-1) mg protein(-1)) and PGE2 (0.3+/-0.1 microl min(-1) mg protein(-1)) in LC-MS/MS analysis. We conclude that OCT2h is not capable of transporting prostaglandins. The data from the previous report may represent binding rather than transport. Our comparison of transport efficiencies confirms the notion that relevant substrates of OCT1, OCT2, and EMT must carry a positive charge.
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PMID:Are organic cation transporters capable of transporting prostaglandins? 1621 6