title: Extended exposure to substrate regulates the human equilibrative nucleoside transporter 1 (hENT1).
abstract: Human equilibrative nucleoside transporter 1 (hENT1) is a major route of entry of nucleosides and nucleoside analog drugs. The regulation of hENT1 is poorly understood in spite of its clinical importance as a drug transporter. Immunofluorescence microscopy and fluorescence-activated cell sorting suggested that cytidine pre-treatment (40 μM, 6 h) promotes hENT1 internalization in a way that does not affect either hENT1-mediated nucleoside uptake or gemcitabine-induced cytotoxicity. The Scatchard plot analyses of our NBTI binding data support previous speculations that hENT1 proteins exist as two sub-populations, and suggest that cytidine pre-treatment leads to the internalization of one population.
authors.affiliation: a Department of Chemistry and Biology , Ryerson University , Toronto , Canada.
authors.forename: Maliha
authors.initials: M
authors.lastname: Zafar
authors.affiliation: a Department of Chemistry and Biology , Ryerson University , Toronto , Canada.
authors.forename: Zlatina
authors.initials: Z
authors.lastname: Naydenova
authors.affiliation: a Department of Chemistry and Biology , Ryerson University , Toronto , Canada.
authors.forename: Imogen R
authors.initials: IR
authors.lastname: Coe
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001665:Binding Sites; D003562:Cytidine / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D033721:Equilibrative Nucleoside Transporter 1 / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D021381:Protein Transport; D013868:Thioinosine / Q000031:analogs & derivatives / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D033721:Equilibrative Nucleoside Transporter 1; C438649:SLC29A1 protein, human; D003841:Deoxycytidine; D013868:Thioinosine; D003562:Cytidine; C001789:4-nitrobenzylthioinosine; D000093542:Gemcitabine
keywords: Anticancer nucleosides; ENT1; cytidine; gemcitabine; regulation