Inhibition of PARG activity affects lysosomal function and hampers T. cruzi infection in Vero cells

Autores
Chiatellino, Maria Clara; Svagzdys, Ailin; Fernandez Villamil, Silvia Hebe; Vilchez Larrea, Salomé Catalina
Año de publicación
2020
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Chagas disease is a potentially life-threatening protozoan infection with little therapeuticalternatives. Since Trypanosoma cruzi triggers different host cell signaling pathways, targetingthem can be therapeutically valuable. Poly(ADP-ribose) (PAR) participates in host cell responseduring the infection: Poly(ADP-ribose)Polymease-1 inhibition or silencing decreases T .cruziinfection and Poly(ADP-ribose)glycohyrolase (PARG) inhibition or silencing almost completelyabrogates it. New results showed PAR raised early after infection (15 min) and remainedelevated. T. cruzi invades the host cell by lysosome-independent, lysosome-dependent orautophagic pathways. However, they must all culminate in the fusion of the trypomastigotebearingparasitophorous vacuole (TcPV) to lysosomes. PARG inhibition or silencing during theinvasion step caused a significant reduction in T. cruzi cell invasion. Absence of PARG activitydidn ́t hamper formation of TcPV with early endosomal characteristics (EEA1+ or PIP3+vacuoles), nor infection levels under nutritional stress, suggesting PARG is unimportant in earlylysosome-independent and autophagic pathways. However, PARG activity seems crucial forlysosomal function: PARG-silenced or inhibited cells reduced DQ-BSA Red and LysotrackerDND-99 staining, indicating proteolytic activity and pH are altered. LAMP-1 signal was alsodrastically reduced. PARG activity seems important for the maintenance of lysosomal activity,and, therefore, for the initial steps of T. cruzi infection.
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: Svagzdys, Ailin. 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
Parasitravaganza
Smithfield
Australia
Australian Society for Parasitology
Materia
Trypanosoma cruzi
Poly ADP-ribose
Invasion
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:11336/201899
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/201899
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inhibition of PARG activity affects lysosomal function and hampers T. cruzi infection in Vero cellsChiatellino, Maria ClaraSvagzdys, AilinFernandez Villamil, Silvia HebeVilchez Larrea, Salomé CatalinaTrypanosoma cruziPoly ADP-riboseInvasionLysosomeshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Chagas disease is a potentially life-threatening protozoan infection with little therapeuticalternatives. Since Trypanosoma cruzi triggers different host cell signaling pathways, targetingthem can be therapeutically valuable. Poly(ADP-ribose) (PAR) participates in host cell responseduring the infection: Poly(ADP-ribose)Polymease-1 inhibition or silencing decreases T .cruziinfection and Poly(ADP-ribose)glycohyrolase (PARG) inhibition or silencing almost completelyabrogates it. New results showed PAR raised early after infection (15 min) and remainedelevated. T. cruzi invades the host cell by lysosome-independent, lysosome-dependent orautophagic pathways. However, they must all culminate in the fusion of the trypomastigotebearingparasitophorous vacuole (TcPV) to lysosomes. PARG inhibition or silencing during theinvasion step caused a significant reduction in T. cruzi cell invasion. Absence of PARG activitydidn ́t hamper formation of TcPV with early endosomal characteristics (EEA1+ or PIP3+vacuoles), nor infection levels under nutritional stress, suggesting PARG is unimportant in earlylysosome-independent and autophagic pathways. However, PARG activity seems crucial forlysosomal function: PARG-silenced or inhibited cells reduced DQ-BSA Red and LysotrackerDND-99 staining, indicating proteolytic activity and pH are altered. LAMP-1 signal was alsodrastically reduced. PARG activity seems important for the maintenance of lysosomal activity,and, therefore, for the initial steps of T. cruzi infection.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: Svagzdys, Ailin. 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"; ArgentinaParasitravaganzaSmithfieldAustraliaAustralian Society for ParasitologyAustralian Society for Parasitology2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectConferenciaBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/201899Inhibition of PARG activity affects lysosomal function and hampers T. cruzi infection in Vero cells; Parasitravaganza; Smithfield; Australia; 2020; 93-93CONICET DigitalCONICETenginfo:eu-repo/semantics/reference/url/https://ri.conicet.gov.ar/handle/11336/154738info:eu-repo/semantics/altIdentifier/url/https://www.parasite.org.au/wp-content/uploads/2020/07/Parasitravaganza-Program-Booklet-2.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 Técnicas2025-09-29T10:41:37Zoai:ri.conicet.gov.ar:11336/201899instacron: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 10:41:37.562CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibition of PARG activity affects lysosomal function and hampers T. cruzi infection in Vero cells
title Inhibition of PARG activity affects lysosomal function and hampers T. cruzi infection in Vero cells
spellingShingle Inhibition of PARG activity affects lysosomal function and hampers T. cruzi infection in Vero cells
Chiatellino, Maria Clara
Trypanosoma cruzi
Poly ADP-ribose
Invasion
Lysosomes
title_short Inhibition of PARG activity affects lysosomal function and hampers T. cruzi infection in Vero cells
title_full Inhibition of PARG activity affects lysosomal function and hampers T. cruzi infection in Vero cells
title_fullStr Inhibition of PARG activity affects lysosomal function and hampers T. cruzi infection in Vero cells
title_full_unstemmed Inhibition of PARG activity affects lysosomal function and hampers T. cruzi infection in Vero cells
title_sort Inhibition of PARG activity affects lysosomal function and hampers T. cruzi infection in Vero cells
dc.creator.none.fl_str_mv Chiatellino, Maria Clara
Svagzdys, Ailin
Fernandez Villamil, Silvia Hebe
Vilchez Larrea, Salomé Catalina
author Chiatellino, Maria Clara
author_facet Chiatellino, Maria Clara
Svagzdys, Ailin
Fernandez Villamil, Silvia Hebe
Vilchez Larrea, Salomé Catalina
author_role author
author2 Svagzdys, Ailin
Fernandez Villamil, Silvia Hebe
Vilchez Larrea, Salomé Catalina
author2_role author
author
author
dc.subject.none.fl_str_mv Trypanosoma cruzi
Poly ADP-ribose
Invasion
Lysosomes
topic Trypanosoma cruzi
Poly ADP-ribose
Invasion
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 is a potentially life-threatening protozoan infection with little therapeuticalternatives. Since Trypanosoma cruzi triggers different host cell signaling pathways, targetingthem can be therapeutically valuable. Poly(ADP-ribose) (PAR) participates in host cell responseduring the infection: Poly(ADP-ribose)Polymease-1 inhibition or silencing decreases T .cruziinfection and Poly(ADP-ribose)glycohyrolase (PARG) inhibition or silencing almost completelyabrogates it. New results showed PAR raised early after infection (15 min) and remainedelevated. T. cruzi invades the host cell by lysosome-independent, lysosome-dependent orautophagic pathways. However, they must all culminate in the fusion of the trypomastigotebearingparasitophorous vacuole (TcPV) to lysosomes. PARG inhibition or silencing during theinvasion step caused a significant reduction in T. cruzi cell invasion. Absence of PARG activitydidn ́t hamper formation of TcPV with early endosomal characteristics (EEA1+ or PIP3+vacuoles), nor infection levels under nutritional stress, suggesting PARG is unimportant in earlylysosome-independent and autophagic pathways. However, PARG activity seems crucial forlysosomal function: PARG-silenced or inhibited cells reduced DQ-BSA Red and LysotrackerDND-99 staining, indicating proteolytic activity and pH are altered. LAMP-1 signal was alsodrastically reduced. PARG activity seems important for the maintenance of lysosomal activity,and, therefore, for the initial steps of T. cruzi infection.
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: Svagzdys, Ailin. 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
Parasitravaganza
Smithfield
Australia
Australian Society for Parasitology
description Chagas disease is a potentially life-threatening protozoan infection with little therapeuticalternatives. Since Trypanosoma cruzi triggers different host cell signaling pathways, targetingthem can be therapeutically valuable. Poly(ADP-ribose) (PAR) participates in host cell responseduring the infection: Poly(ADP-ribose)Polymease-1 inhibition or silencing decreases T .cruziinfection and Poly(ADP-ribose)glycohyrolase (PARG) inhibition or silencing almost completelyabrogates it. New results showed PAR raised early after infection (15 min) and remainedelevated. T. cruzi invades the host cell by lysosome-independent, lysosome-dependent orautophagic pathways. However, they must all culminate in the fusion of the trypomastigotebearingparasitophorous vacuole (TcPV) to lysosomes. PARG inhibition or silencing during theinvasion step caused a significant reduction in T. cruzi cell invasion. Absence of PARG activitydidn ́t hamper formation of TcPV with early endosomal characteristics (EEA1+ or PIP3+vacuoles), nor infection levels under nutritional stress, suggesting PARG is unimportant in earlylysosome-independent and autophagic pathways. However, PARG activity seems crucial forlysosomal function: PARG-silenced or inhibited cells reduced DQ-BSA Red and LysotrackerDND-99 staining, indicating proteolytic activity and pH are altered. LAMP-1 signal was alsodrastically reduced. PARG activity seems important for the maintenance of lysosomal activity,and, therefore, for the initial steps of T. cruzi infection.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Conferencia
Book
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/11336/201899
Inhibition of PARG activity affects lysosomal function and hampers T. cruzi infection in Vero cells; Parasitravaganza; Smithfield; Australia; 2020; 93-93
CONICET Digital
CONICET
url http://hdl.handle.net/11336/201899
identifier_str_mv Inhibition of PARG activity affects lysosomal function and hampers T. cruzi infection in Vero cells; Parasitravaganza; Smithfield; Australia; 2020; 93-93
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/reference/url/https://ri.conicet.gov.ar/handle/11336/154738
info:eu-repo/semantics/altIdentifier/url/https://www.parasite.org.au/wp-content/uploads/2020/07/Parasitravaganza-Program-Booklet-2.pdf
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Australian Society for Parasitology
publisher.none.fl_str_mv Australian Society for Parasitology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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