Poly(ADP-ribose)Glycohydrolase activity is important for lysosome formation during Trypanosoma cruzi invasion

Autores
Chiatellino, Maria Clara; Fernandez Villamil, Silvia Hebe; Vilchez Larrea, Salomé Catalina
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Chagas´ disease stands as one of the main public health problems in Latin America. T. cruzi, protozoan parasite responsible for this disease, has a complex life cycle comprising several stages that allow it to multiply and disseminate. During the cell invasion step, the parasite modulates several metabolic pathways in the host cell; therefore, drugs that operate on these pathways could be used with therapeutic aims. Signaling though PI3k/Akt elicited in the host cell during T. cruzi infection. Activation of this pathway is important since it has anti-apoptotic effects that operate in favor of the infection and is also crucial for the regulation of the lysosome dependent and independent invasion mechanisms. Recently, it has been reported that Poly(ADP-ribose)Glycohydrolase (PARG) participates in the regulation of the PI3k/Akt route by downregulating Akt phosphorylation in cancer cells. In our infection model, PARG inhibition by DEA 1 μM or silencing by iRNA (shPARG) in Vero cells, the % of phosphorylated Akt is not altered when compared to Wild Type infected cells, but the upregulation of Akt levels on Wild Type (35% at 15 min and 80% at 6 h PI) cells could not be observed in cells where PARG activity is absent. Lysosome formation in response to parasitic infection is also altered when Vero cell PARG is inhibited or silenced: at 1 h PI, LAMP-1 (lysosome marker) signaling diminishes in DEA 1 μM-treated or shPARG cells in comparison to Wild Type cells. The reduction in lysosome density can also been observed in the absence of infection, indicating that lysosome formation regulation by PARG might be operating also in physiological conditions. Previous results obtained by our group showed that PARG inhibition led to a marked decrease in T. cruzi infection in vitro. These new findings could indicate that the downregulation of the lysosome invasion pathway could partially account for the reduction in T. cruzi infection when PARG activity is absent.
Fil: Chiatellino, Maria Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Fernandez Villamil, Silvia Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Vilchez Larrea, Salomé Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Ministerio de Ciencia. Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica; Argentina
LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
The Histochemical Society
Materia
TRYPANOSOMA CRUZI
PARG
INVASIÓN
LYSOSOMES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/234137

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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Poly(ADP-ribose)Glycohydrolase activity is important for lysosome formation during Trypanosoma cruzi invasionChiatellino, Maria ClaraFernandez Villamil, Silvia HebeVilchez Larrea, Salomé CatalinaTRYPANOSOMA CRUZIPARGINVASIÓNLYSOSOMEShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Chagas´ disease stands as one of the main public health problems in Latin America. T. cruzi, protozoan parasite responsible for this disease, has a complex life cycle comprising several stages that allow it to multiply and disseminate. During the cell invasion step, the parasite modulates several metabolic pathways in the host cell; therefore, drugs that operate on these pathways could be used with therapeutic aims. Signaling though PI3k/Akt elicited in the host cell during T. cruzi infection. Activation of this pathway is important since it has anti-apoptotic effects that operate in favor of the infection and is also crucial for the regulation of the lysosome dependent and independent invasion mechanisms. Recently, it has been reported that Poly(ADP-ribose)Glycohydrolase (PARG) participates in the regulation of the PI3k/Akt route by downregulating Akt phosphorylation in cancer cells. In our infection model, PARG inhibition by DEA 1 μM or silencing by iRNA (shPARG) in Vero cells, the % of phosphorylated Akt is not altered when compared to Wild Type infected cells, but the upregulation of Akt levels on Wild Type (35% at 15 min and 80% at 6 h PI) cells could not be observed in cells where PARG activity is absent. Lysosome formation in response to parasitic infection is also altered when Vero cell PARG is inhibited or silenced: at 1 h PI, LAMP-1 (lysosome marker) signaling diminishes in DEA 1 μM-treated or shPARG cells in comparison to Wild Type cells. The reduction in lysosome density can also been observed in the absence of infection, indicating that lysosome formation regulation by PARG might be operating also in physiological conditions. Previous results obtained by our group showed that PARG inhibition led to a marked decrease in T. cruzi infection in vitro. These new findings could indicate that the downregulation of the lysosome invasion pathway could partially account for the reduction in T. cruzi infection when PARG activity is absent.Fil: Chiatellino, Maria Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Fernandez Villamil, Silvia Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Vilchez Larrea, Salomé Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Ministerio de Ciencia. Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica; ArgentinaLXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioMar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioThe Histochemical SocietyFundación Revista Medicina2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/234137Poly(ADP-ribose)Glycohydrolase activity is important for lysosome formation during Trypanosoma cruzi invasion; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 181-1810025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://medicinabuenosaires.com/revistas/vol79-19/s4/vol79_s4.pdfInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:49:17Zoai:ri.conicet.gov.ar:11336/234137instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:49:17.451CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Poly(ADP-ribose)Glycohydrolase activity is important for lysosome formation during Trypanosoma cruzi invasion
title Poly(ADP-ribose)Glycohydrolase activity is important for lysosome formation during Trypanosoma cruzi invasion
spellingShingle Poly(ADP-ribose)Glycohydrolase activity is important for lysosome formation during Trypanosoma cruzi invasion
Chiatellino, Maria Clara
TRYPANOSOMA CRUZI
PARG
INVASIÓN
LYSOSOMES
title_short Poly(ADP-ribose)Glycohydrolase activity is important for lysosome formation during Trypanosoma cruzi invasion
title_full Poly(ADP-ribose)Glycohydrolase activity is important for lysosome formation during Trypanosoma cruzi invasion
title_fullStr Poly(ADP-ribose)Glycohydrolase activity is important for lysosome formation during Trypanosoma cruzi invasion
title_full_unstemmed Poly(ADP-ribose)Glycohydrolase activity is important for lysosome formation during Trypanosoma cruzi invasion
title_sort Poly(ADP-ribose)Glycohydrolase activity is important for lysosome formation during Trypanosoma cruzi invasion
dc.creator.none.fl_str_mv Chiatellino, Maria Clara
Fernandez Villamil, Silvia Hebe
Vilchez Larrea, Salomé Catalina
author Chiatellino, Maria Clara
author_facet Chiatellino, Maria Clara
Fernandez Villamil, Silvia Hebe
Vilchez Larrea, Salomé Catalina
author_role author
author2 Fernandez Villamil, Silvia Hebe
Vilchez Larrea, Salomé Catalina
author2_role author
author
dc.subject.none.fl_str_mv TRYPANOSOMA CRUZI
PARG
INVASIÓN
LYSOSOMES
topic TRYPANOSOMA CRUZI
PARG
INVASIÓN
LYSOSOMES
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Chagas´ disease stands as one of the main public health problems in Latin America. T. cruzi, protozoan parasite responsible for this disease, has a complex life cycle comprising several stages that allow it to multiply and disseminate. During the cell invasion step, the parasite modulates several metabolic pathways in the host cell; therefore, drugs that operate on these pathways could be used with therapeutic aims. Signaling though PI3k/Akt elicited in the host cell during T. cruzi infection. Activation of this pathway is important since it has anti-apoptotic effects that operate in favor of the infection and is also crucial for the regulation of the lysosome dependent and independent invasion mechanisms. Recently, it has been reported that Poly(ADP-ribose)Glycohydrolase (PARG) participates in the regulation of the PI3k/Akt route by downregulating Akt phosphorylation in cancer cells. In our infection model, PARG inhibition by DEA 1 μM or silencing by iRNA (shPARG) in Vero cells, the % of phosphorylated Akt is not altered when compared to Wild Type infected cells, but the upregulation of Akt levels on Wild Type (35% at 15 min and 80% at 6 h PI) cells could not be observed in cells where PARG activity is absent. Lysosome formation in response to parasitic infection is also altered when Vero cell PARG is inhibited or silenced: at 1 h PI, LAMP-1 (lysosome marker) signaling diminishes in DEA 1 μM-treated or shPARG cells in comparison to Wild Type cells. The reduction in lysosome density can also been observed in the absence of infection, indicating that lysosome formation regulation by PARG might be operating also in physiological conditions. Previous results obtained by our group showed that PARG inhibition led to a marked decrease in T. cruzi infection in vitro. These new findings could indicate that the downregulation of the lysosome invasion pathway could partially account for the reduction in T. cruzi infection when PARG activity is absent.
Fil: Chiatellino, Maria Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Fernandez Villamil, Silvia Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Vilchez Larrea, Salomé Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Ministerio de Ciencia. Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica; Argentina
LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
The Histochemical Society
description Chagas´ disease stands as one of the main public health problems in Latin America. T. cruzi, protozoan parasite responsible for this disease, has a complex life cycle comprising several stages that allow it to multiply and disseminate. During the cell invasion step, the parasite modulates several metabolic pathways in the host cell; therefore, drugs that operate on these pathways could be used with therapeutic aims. Signaling though PI3k/Akt elicited in the host cell during T. cruzi infection. Activation of this pathway is important since it has anti-apoptotic effects that operate in favor of the infection and is also crucial for the regulation of the lysosome dependent and independent invasion mechanisms. Recently, it has been reported that Poly(ADP-ribose)Glycohydrolase (PARG) participates in the regulation of the PI3k/Akt route by downregulating Akt phosphorylation in cancer cells. In our infection model, PARG inhibition by DEA 1 μM or silencing by iRNA (shPARG) in Vero cells, the % of phosphorylated Akt is not altered when compared to Wild Type infected cells, but the upregulation of Akt levels on Wild Type (35% at 15 min and 80% at 6 h PI) cells could not be observed in cells where PARG activity is absent. Lysosome formation in response to parasitic infection is also altered when Vero cell PARG is inhibited or silenced: at 1 h PI, LAMP-1 (lysosome marker) signaling diminishes in DEA 1 μM-treated or shPARG cells in comparison to Wild Type cells. The reduction in lysosome density can also been observed in the absence of infection, indicating that lysosome formation regulation by PARG might be operating also in physiological conditions. Previous results obtained by our group showed that PARG inhibition led to a marked decrease in T. cruzi infection in vitro. These new findings could indicate that the downregulation of the lysosome invasion pathway could partially account for the reduction in T. cruzi infection when PARG activity is absent.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
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http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/234137
Poly(ADP-ribose)Glycohydrolase activity is important for lysosome formation during Trypanosoma cruzi invasion; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 181-181
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/234137
identifier_str_mv Poly(ADP-ribose)Glycohydrolase activity is important for lysosome formation during Trypanosoma cruzi invasion; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 181-181
0025-7680
1669-9106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://medicinabuenosaires.com/revistas/vol79-19/s4/vol79_s4.pdf
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