Document Detail


Substrate preferences and glucose uptake in glibenclamide-resistant Leishmania parasites.
MedLine Citation:
PMID:  15886061     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Nestor Luis Uzcategui; Katherine Figarella; Natacha Camacho; Alicia Ponte-Sucre
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  2005-06-10     Completed Date:  2005-09-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100959500     Medline TA:  Comp Biochem Physiol C Toxicol Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  395-402     Citation Subset:  IM    
Affiliation:
Laboratorio de Fisiología Molecular, Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela.
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MeSH Terms
Descriptor/Qualifier:
Alanine Transaminase / 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:
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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