TY - JOUR
T1 - Entamoeba histolytica P-glycoprotein (EhPgp) inhibition, induce trophozoite acidification and enhance programmed cell death
AU - Medel Flores, Olivia
AU - Gómez García, Consuelo
AU - Sánchez Monroy, Virgina
AU - Villalba Magadaleno, José D.Artagnan
AU - Nader García, Elvira
AU - Pérez Ishiwara, D. Guillermo
N1 - Funding Information:
This work was supported by CONACYT and SIP-IPN grants given to D.G.P.I. The authors gratefully acknowledge the collaboration from Dr. Mineko Shibayama’s laboratory at CINVESTAV-IPN, especially the assistance of Angelica Silva-Olivares with transmission electronic microscopy. We thank Dr. Julio Cesar Carrero from Instituto de Biomedicas-UNAM and also to Francisco Javier Paz Bermudez, Chemical Pharmacobiology from CINVESTAV-IPN for kindly support. Finally, we also express our gratitude to Veronica Castillo for graphical design.
PY - 2013/11
Y1 - 2013/11
N2 - 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. Ca2+ concentration was increased, while the intracellular pH (ipH) was acidified. In contrast, PGP overexpression prevented intracellular acidification and circumvented the apoptotic effect of G418.
AB - 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. Ca2+ concentration was increased, while the intracellular pH (ipH) was acidified. In contrast, PGP overexpression prevented intracellular acidification and circumvented the apoptotic effect of G418.
UR - http://www.scopus.com/inward/record.url?scp=84884727309&partnerID=8YFLogxK
U2 - 10.1016/j.exppara.2013.08.017
DO - 10.1016/j.exppara.2013.08.017
M3 - Artículo
SN - 0014-4894
VL - 135
SP - 532
EP - 540
JO - Experimental Parasitology
JF - Experimental Parasitology
IS - 3
ER -