| Substrate preferences and glucose uptake in glibenclamide-resistant Leishmania parasites. | |
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MedLine Citation:
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PMID: 15886061 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Several drug-resistant mammalian cell types exhibit increased glycolytic rates, preferential synthesis of ATP through oxidative phosphorylation, and altered glucose transport. Herein we analyzed the influence of parasite growth phase on energy substrate uptake and use in a Leishmania strain [NR(Gr)] selected for resistance against glibenclamide. Glibenclamide is an ABC-transporter blocker which modulates the function of glucose transporters in some mammalian cells. Our results demonstrate for the first time that compared to glibenclamide-sensitive Leishmania, exponential phase glibenclamide-resistant parasites exhibit decreased use of glucose as energy substrate, decreased glucose uptake and decreased glucose transporter expression. However, compared to glibenclamide-sensitive cells, stationary phase resistant parasites display an increased use of amino acids as energy substrate and an increased activity of the enzymes hexokinase, phosphoglucose isomerase, and especially NAD(+)-linked glutamate dehydrogenase. These results suggest that drug resistance in Leishmania involves a metabolic adaptation that promotes a stage dependent modulation of energy substrate uptake and use as a physiological response to the challenge imposed by drug pressure. |
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Authors:
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Nestor Luis Uzcategui; Katherine Figarella; Natacha Camacho; Alicia Ponte-Sucre |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Comparative biochemistry and physiology. Toxicology & pharmacology : CBP Volume: 140 ISSN: 1532-0456 ISO Abbreviation: Comp. Biochem. Physiol. C Toxicol. Pharmacol. Publication Date: 2005 Mar-Apr |
Date Detail:
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Created Date: 2005-06-10 Completed Date: 2005-09-14 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100959500 Medline TA: Comp Biochem Physiol C Toxicol Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 395-402 Citation Subset: IM |
Affiliation:
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Laboratorio de Fisiología Molecular, Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alanine Transaminase
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metabolism Animals Cytochalasin B / pharmacology Drug Resistance* Glucose / metabolism* Glucose-6-Phosphate Isomerase / metabolism Glutamate Dehydrogenase / metabolism Glyburide / pharmacology* Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism Hexokinase / metabolism Leishmania / drug effects*, metabolism* Monosaccharide Transport Proteins / metabolism Substrate Specificity |
| Chemical | |
Reg. No./Substance:
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0/Monosaccharide Transport Proteins; 10238-21-8/Glyburide; 14930-96-2/Cytochalasin B; 50-99-7/Glucose; EC 1.2.1.-/Glyceraldehyde-3-Phosphate Dehydrogenases; EC 1.4.1.2/Glutamate Dehydrogenase; EC 2.6.1.2/Alanine Transaminase; EC 2.7.1.1/Hexokinase; EC 5.3.1.9/Glucose-6-Phosphate Isomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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