dc.creatorUzcátegui, Néstor L.
dc.creatorFigarella, Katherine
dc.creatorCamacho, Natacha
dc.creatorPonte-Sucre, Alicia
dc.date2012-08-23T23:49:27Z
dc.date2012-08-23T23:49:27Z
dc.date2012-08-23
dc.date.accessioned2022-10-28T00:50:28Z
dc.date.available2022-10-28T00:50:28Z
dc.identifier1532-0456
dc.identifierhttp://hdl.handle.net/10872/1704
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/4936319
dc.descriptionSeveral 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.
dc.descriptionConsejo de Desarrollo Cientifico y Humanistico UCV, Coordinacion de Investgiacion de la Facultad de Medicina, UCV
dc.languageen_US
dc.relationComparative Biochemistry and Physiology;140:395-402, 2005
dc.subjectAmino acid
dc.subjectDrug resistance
dc.subjectGlucose uptake
dc.subjectLeishmania
dc.subjectMetabolic substrate
dc.titleSubstrate preferences and glucose uptake in glibenclamide-resistant Leishmania parasites
dc.typeArticle


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