title: Entamoeba histolytica P-glycoprotein (EhPgp) inhibition, induce trophozoite acidification and enhance programmed cell death.
abstract: Programmed cell death (PCD) is induced in Entamoeba histolytica by a variety of stimuli in vitro and in vivo. In mammals, intracellular acidification serves as a global switch for inactivating cellular processes and initiates molecular mechanisms implicated in the destruction of the genome. In contrast, intracellular alkalinization produced by P-glycoprotein overexpression in multidrug-resistant cells has been related to apoptosis resistance. Our previous studies showed that overexpression of E. histolytica P-glycoprotein (PGP) altered chloride-dependent currents and triggered trophozoite swelling, the reverse process of cell shrinkage produced during PCD. Here we showed that antisense inhibition of PGP expression produced a synchronous death of trophozoites and the enhancement of biochemical and morphological characteristics of PCD induced by G418. The nucleus was contracted, and the nuclear membrane was disrupted. Moreover, chromatin was extensively fragmented. Ca(2+) concentration was increased, while the intracellular pH (ipH) was acidified. In contrast, PGP overexpression prevented intracellular acidification and circumvented the apoptotic effect of G418.
authors.affiliation: Programa Institucional de Biomedicina Molecular ENMyH, Instituto Politécnico Nacional, Guillermo Massieu Helguera No. 239, CP 07320, México DF, Mexico.
authors.forename: Olivia
authors.initials: O
authors.lastname: Medel Flores
authors.forename: Consuelo
authors.initials: C
authors.lastname: Gómez García
authors.forename: Virgina
authors.initials: V
authors.lastname: Sánchez Monroy
authors.forename: José D'Artagnan
authors.initials: JD
authors.lastname: Villalba Magadaleno
authors.forename: Elvira
authors.initials: E
authors.lastname: Nader García
authors.forename: D Guillermo
authors.initials: DG
authors.lastname: Pérez Ishiwara
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000563:Amebicides / Q000494:pharmacology*; D016375:Antisense Elements (Genetics) / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D004748:Entamoeba histolytica / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015870:Gene Expression; D005839:Gentamicins / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D010957:Plasmids; D014162:Transfection; D053058:Trophozoites / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000563:Amebicides; D016375:Antisense Elements (Genetics); D005839:Gentamicins; C010680:antibiotic G 418