Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

J774 macrophage-like cells express organic anion transporters that promote the efflux of fluoroquinolone antibiotics such as norfloxacin (NFX) from these cells. Gemfibrozil (GFZ) blocks organic anion transport in J774 cells, thereby facilitating the intracellular accumulation of NFX (Cao, C., H.C. Neu, and S.C. Silverstein. 1991. J. Cell Biol. 115:467a [Abstr.]). To determine whether GFZ enhances the efficacy of fluoroquinolone antibiotics against intracellular bacterial pathogens, J774 cells were infected with Listeria monocytogenes and incubated in medium containing a fluoroquinolone antibiotic in the presence or absence of GFZ. Intracellular growth of L. monocytogenes was evaluated by lysing J774 cells and assaying for colony-forming units of Listeria. GFZ intensified the bacteriostatic effect of 4 micrograms/ml NFX and rendered 8 micrograms/ml bactericidal for L. monocytogenes. GFZ had a similar potentiating effect when used in combination with 2 micrograms/ml ciprofloxacin (CFX). CFX plus GFZ was bactericidal for intracellular L. monocytogenes. Treatment of J774 cells with NFX plus GFZ markedly reduced the cytotoxic effect of the bacteria on these cells. Over 55% of cells treated with 8 micrograms/ml NFX alone were dead 16 h after infection, whereas only 5% of cells treated with 8 micrograms/ml NFX plus GFZ were dead at 16 h. Similarly, GFZ potentiated the ability of 2 micrograms/ml to protect J774 cells against the cytocidal effect of Listeria. NFX in combination with GFZ limited cell-to-cell spread of L. monocytogenes. In antibiotic-free medium, > 99% of J774 cells contained intracellular L. monocytogenes at 14 h after infection. NFX alone in the medium did not change this outcome. However, 4 micrograms/ml NFX plus GFZ decreased bacterial spread by approximately 40% at 24 h postinfection, and 8 micrograms/ml NFX plus GFZ prevented all spread beyond the initially infected cell population. These results suggest that GFZ could be used clinically to enhance the efficacy of fluoroquinolone and of other anionic antibiotics against bacteria that grow and/or reside within macrophages and/or other cells.
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PMID:Gemfibrozil enhances the listeriacidal effects of fluoroquinolone antibiotics in J774 macrophages. 140 86

Fibrates are hypolipidemic pharmaceuticals that have been detected as contaminants in wastewaters and surface waters. In this work, the possible effects of two fibrates, Bezafibrate (BEZA) and Gemfibrozil (GEM) in the bivalve mollusc Mytilus spp were investigated. In the immune cells, the hemocytes, addition of both compounds in vitro induced rapid lysosomal membrane destabilization, extracellular lysozyme release, NO production and decreased phagocytic activity. The effect of fibrates were partly mediated by activation of ERK and p38 MAPKs (Mitogen Activated Protein Kinases), as demonstrated by the use of specific inhibitors of different kinases. The effects of fibrates on hemocyte function were confirmed in vivo, in the hemocytes of mussels injected with 0.01, 0.1 and 1 nmol/animal (corresponding to nominal concentrations of 3.61, 36.18 and 361.8ng/g dry weight for BEZA and of 2.50, 25.03 and 250.35 ng/g dry weight for GEM, respectively) and sampled at 24h post-injection. Both compounds induced a concentration-dependent lysosomal destabilization and extracellular lysozyme release; an increase in phagocytosis was observed at the highest concentration. In vivo exposure to fibrates also induced significant effects on mussel digestive gland, the key metabolic organ in bivalves. Both BEZA and GEM increased the activity of the glycolytic enzymes phosphofructokinase (PFK) and pyruvate kinase (PK), and of Glutathione transferase (GST) glutathione reductase (GSR), and total glutathione content. A significant increase in the peroxisomal enzyme catalase was observed; however, BEZA exposure decreased Palmytoyl CoA oxidase activity, whereas GEM was ineffective. The results indicate that in mussels environmental concentrations of hypolipidemic drugs can affect the immune function, as well as glycolysis, redox balance and peroxisomal function.
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PMID:Effects of blood lipid lowering pharmaceuticals (bezafibrate and gemfibrozil) on immune and digestive gland functions of the bivalve mollusc, Mytilus galloprovincialis. 1757 95