Potential Role of Sodium-Proton Exchangers in the Low Concentration Arsenic Trioxide-Increased Intracellular pH and Cell Proliferation

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dc.contributor.authorAravena, Carmen
dc.contributor.authorBeltran, Ana R.
dc.contributor.authorCornejo, Marcelo
dc.contributor.authorTorres, Viviana
dc.contributor.authorDiaz, Emilce S.
dc.contributor.authorGuzman Gutierrez, Enrique
dc.contributor.authorPardo, Fabian
dc.contributor.authorLeiva, Andrea
dc.contributor.authorSobrevia, Luis
dc.contributor.authorRamirez, Marco A.
dc.date.accessioned2024-01-10T13:52:17Z
dc.date.available2024-01-10T13:52:17Z
dc.date.issued2012
dc.description.abstractArsenic main inorganic compound is arsenic trioxide (ATO) presented in solution mainly as arsenite. ATO increases intracellular pH (pHi), cell proliferation and tumor growth. Sodium-proton exchangers (NHEs) modulate the pHi, with NHE1 playing significant roles. Whether ATO-increased cell proliferation results from altered NHEs expression and activity is unknown. We hypothesize that ATO increases cell proliferation by altering pHi due to increased NHEs-like transport activity. Madin-Darby canine kidney (MDCK) cells grown in 5 mmol/L D-glucose-containing DMEM were exposed to ATO (0.05, 0.5 or 5 mu mol/L, 0-48 hours) in the absence or presence of 5-N, N-hexamethylene amiloride (HMA, 5-100 mu mol/L, NHEs inhibitor), PD-98059 (30 mu mol/L, MAPK1/2 inhibitor), Go6976 (10 mu mol/L, PKC alpha, beta I and mu inhibitor), or Schering 28080 (10 mu mol/L, H+/K(+)ATPase inhibitor) plus concanamycin (0.1 mu mol/L, V type ATPases inhibitor). Incorporation of [H-3]thymidine was used to estimate cell proliferation, and counting cells with a hemocytometer to determine the cell number. The pHi was measured by fluorometry in 2,7-bicarboxyethyl-5,6-carboxyfluorescein loaded cells. The Na+-dependent HMA-sensitive NHEs-like mediated proton transport kinetics, NHE1 protein abundance in the total, cytoplasm and plasma membrane protein fractions, and phosphorylated and total p42/44 mitogen-activated protein kinases (p42/44(mapk)) were also determined. Lowest ATO (0.05 mu mol/L, similar to 0.01 ppm) used in this study increased cell proliferation, pHi, NHEs-like transport and plasma membrane NHE1 protein abundance, effects blocked by HMA, PD-98059 or Go6976. Cell-buffering capacity did not change by ATO. The results show that a low ATO concentration increases MDCK cells proliferation by NHEs (probably NHE1)-like transport dependent-increased pHi requiring p42/44(mapk) and PKC alpha, beta I and/or mu activity. This finding could be crucial in diseases where uncontrolled cell growth occurs, such as tumor growth, and in circumstances where ATO, likely arsenite, is available at the drinking-water at these levels. Citation: Aravena C, Beltran AR, Cornejo M, Torres V, Diaz ES, et al. (2012) Potential Role of Sodium-Proton Exchangers in the Low Concentration Arsenic Trioxide-Increased Intracellular pH and Cell Proliferation. PLoS ONE 7(12): e51451. doi:10.1371/journal.pone.0051451
dc.description.funderDireccion de Investigacion
dc.description.funderVicerrectoria Academica, Universidad de Antofagasta (Chile)
dc.description.funderFondo Nacional de Desarrollo Cientifico y Tecnologico
dc.description.funderPrograma de Investigacion Interdisciplinario (PIA) from Comision Nacional de Investigacion en Ciencia y Tecnologia (CONICYT) (Chile)
dc.description.funderCONICYT Ayuda de Tesis
dc.format.extent12 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1371/journal.pone.0051451
dc.identifier.issn1932-6203
dc.identifier.pubmedidMEDLINE:23236503
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0051451
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/79655
dc.identifier.wosidWOS:000312589700041
dc.information.autorucCiencias Biológicas;Guzman E ;S/I;197588
dc.information.autorucMedicina;Leiva A ;S/I;3362
dc.information.autorucMedicina;Pardo F ;S/I;1004392
dc.information.autorucCiencias Biológicas;Ramirez M;S/I;101688
dc.information.autorucMedicina;Sobrevia L ;S/I;1002656
dc.issue.numero12
dc.language.isoen
dc.nota.accesoSin adjunto
dc.publisherPUBLIC LIBRARY SCIENCE
dc.revistaPLOS ONE
dc.rightsregistro bibliográfico
dc.subjectEPITHELIAL DOME FORMATION
dc.subjectVEIN ENDOTHELIAL-CELLS
dc.subjectPROTEIN-KINASE-C
dc.subjectNA+/H+ EXCHANGER
dc.subjectCANCER CELLS
dc.subjectNHE3 EXPRESSION
dc.subjectDRINKING-WATER
dc.subjectSMOOTH-MUSCLE
dc.subjectDNA-SYNTHESIS
dc.subjectNITRIC-OXIDE
dc.subject.ods03 Good Health and Well-being
dc.subject.ods06 Clean Water and Sanitation
dc.subject.odspa03 Salud y bienestar
dc.subject.odspa06 Agua limpia y saneamiento
dc.titlePotential Role of Sodium-Proton Exchangers in the Low Concentration Arsenic Trioxide-Increased Intracellular pH and Cell Proliferation
dc.typeartículo
dc.volumen7
sipa.codpersvinculados197588
sipa.codpersvinculados3362
sipa.codpersvinculados1004392
sipa.codpersvinculados101688
sipa.codpersvinculados1002656
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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