A glucosylceramide synthase inhibitor prevents the cytotoxic effects of Shiga toxin-2 on human renal tubular epithelial cells

Autores
Silberstein, Claudia Marcela; Copeland, Diane P; Chiang, Wei Lien; Repetto, Horacio A.; Ibarra, Cristina Adriana
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Shiga toxin-2 binds to the globotriaosyl-ceramide receptor on the plasma membrane of target cells. The highlevel expression of this receptor in renal epithelial cells may account, at least in part, for acute renal failure observed inchildren with hemolytic uremic syndrome. The cytotoxic effect of Shiga toxin-2 was assayed on primary cultures of humanrenal tubular epithelial cells treated with a new specific inhibitor of glucosylceramide synthase (C-9), the ratelimitingfirst step in the glycosphingolipid biosynthetic pathway. The treatment of the cells with 1-5 M C-9 for at least24 h significantly neutralized the action of 1 ng/ml Shiga toxin-2 on cell viability. The expression levels of globotriaosylceramidesignificantly decreased when cells were incubated with 1 M C-9 for 48 h. We propose here that prevention ofglobotriaosyl-ceramide synthesis by the C-9 could be a novel substrate inhibition therapy to neutralize Shiga toxin-2 actionin renal epithelial cells.
Fil: Silberstein, Claudia Marcela. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Copeland, Diane P. No especifíca;
Fil: Chiang, Wei Lien. No especifíca;
Fil: Repetto, Horacio A.. Hospital Nacional Profesor Alejandro Posadas; Argentina
Fil: Ibarra, Cristina Adriana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Materia
Shiga toxin
proximal tubule epithelial cells
globotriaosyl-ceramide
glucosylceramide synthase
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:11336/152947
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/152947
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A glucosylceramide synthase inhibitor prevents the cytotoxic effects of Shiga toxin-2 on human renal tubular epithelial cellsSilberstein, Claudia MarcelaCopeland, Diane PChiang, Wei LienRepetto, Horacio A.Ibarra, Cristina AdrianaShiga toxinproximal tubule epithelial cellsglobotriaosyl-ceramideglucosylceramide synthasehttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Shiga toxin-2 binds to the globotriaosyl-ceramide receptor on the plasma membrane of target cells. The highlevel expression of this receptor in renal epithelial cells may account, at least in part, for acute renal failure observed inchildren with hemolytic uremic syndrome. The cytotoxic effect of Shiga toxin-2 was assayed on primary cultures of humanrenal tubular epithelial cells treated with a new specific inhibitor of glucosylceramide synthase (C-9), the ratelimitingfirst step in the glycosphingolipid biosynthetic pathway. The treatment of the cells with 1-5 M C-9 for at least24 h significantly neutralized the action of 1 ng/ml Shiga toxin-2 on cell viability. The expression levels of globotriaosylceramidesignificantly decreased when cells were incubated with 1 M C-9 for 48 h. We propose here that prevention ofglobotriaosyl-ceramide synthesis by the C-9 could be a novel substrate inhibition therapy to neutralize Shiga toxin-2 actionin renal epithelial cells.Fil: Silberstein, Claudia Marcela. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Copeland, Diane P. No especifíca;Fil: Chiang, Wei Lien. No especifíca;Fil: Repetto, Horacio A.. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Ibarra, Cristina Adriana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaBentham Science Publishers2008-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/152947Silberstein, Claudia Marcela; Copeland, Diane P; Chiang, Wei Lien; Repetto, Horacio A.; Ibarra, Cristina Adriana; A glucosylceramide synthase inhibitor prevents the cytotoxic effects of Shiga toxin-2 on human renal tubular epithelial cells; Bentham Science Publishers; Journal of Epithelial Biology and Pharmacology; 1; 12-2008; 71-751875-0443CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://benthamopen.com/contents/pdf/JEBP/JEBP-1-71.pdfinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:45:02Zoai:ri.conicet.gov.ar:11336/152947instacron: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:34982025-09-03 09:45:02.977CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A glucosylceramide synthase inhibitor prevents the cytotoxic effects of Shiga toxin-2 on human renal tubular epithelial cells
title A glucosylceramide synthase inhibitor prevents the cytotoxic effects of Shiga toxin-2 on human renal tubular epithelial cells
spellingShingle A glucosylceramide synthase inhibitor prevents the cytotoxic effects of Shiga toxin-2 on human renal tubular epithelial cells
Silberstein, Claudia Marcela
Shiga toxin
proximal tubule epithelial cells
globotriaosyl-ceramide
glucosylceramide synthase
title_short A glucosylceramide synthase inhibitor prevents the cytotoxic effects of Shiga toxin-2 on human renal tubular epithelial cells
title_full A glucosylceramide synthase inhibitor prevents the cytotoxic effects of Shiga toxin-2 on human renal tubular epithelial cells
title_fullStr A glucosylceramide synthase inhibitor prevents the cytotoxic effects of Shiga toxin-2 on human renal tubular epithelial cells
title_full_unstemmed A glucosylceramide synthase inhibitor prevents the cytotoxic effects of Shiga toxin-2 on human renal tubular epithelial cells
title_sort A glucosylceramide synthase inhibitor prevents the cytotoxic effects of Shiga toxin-2 on human renal tubular epithelial cells
dc.creator.none.fl_str_mv Silberstein, Claudia Marcela
Copeland, Diane P
Chiang, Wei Lien
Repetto, Horacio A.
Ibarra, Cristina Adriana
author Silberstein, Claudia Marcela
author_facet Silberstein, Claudia Marcela
Copeland, Diane P
Chiang, Wei Lien
Repetto, Horacio A.
Ibarra, Cristina Adriana
author_role author
author2 Copeland, Diane P
Chiang, Wei Lien
Repetto, Horacio A.
Ibarra, Cristina Adriana
author2_role author
author
author
author
dc.subject.none.fl_str_mv Shiga toxin
proximal tubule epithelial cells
globotriaosyl-ceramide
glucosylceramide synthase
topic Shiga toxin
proximal tubule epithelial cells
globotriaosyl-ceramide
glucosylceramide synthase
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Shiga toxin-2 binds to the globotriaosyl-ceramide receptor on the plasma membrane of target cells. The highlevel expression of this receptor in renal epithelial cells may account, at least in part, for acute renal failure observed inchildren with hemolytic uremic syndrome. The cytotoxic effect of Shiga toxin-2 was assayed on primary cultures of humanrenal tubular epithelial cells treated with a new specific inhibitor of glucosylceramide synthase (C-9), the ratelimitingfirst step in the glycosphingolipid biosynthetic pathway. The treatment of the cells with 1-5 M C-9 for at least24 h significantly neutralized the action of 1 ng/ml Shiga toxin-2 on cell viability. The expression levels of globotriaosylceramidesignificantly decreased when cells were incubated with 1 M C-9 for 48 h. We propose here that prevention ofglobotriaosyl-ceramide synthesis by the C-9 could be a novel substrate inhibition therapy to neutralize Shiga toxin-2 actionin renal epithelial cells.
Fil: Silberstein, Claudia Marcela. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Copeland, Diane P. No especifíca;
Fil: Chiang, Wei Lien. No especifíca;
Fil: Repetto, Horacio A.. Hospital Nacional Profesor Alejandro Posadas; Argentina
Fil: Ibarra, Cristina Adriana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
description Shiga toxin-2 binds to the globotriaosyl-ceramide receptor on the plasma membrane of target cells. The highlevel expression of this receptor in renal epithelial cells may account, at least in part, for acute renal failure observed inchildren with hemolytic uremic syndrome. The cytotoxic effect of Shiga toxin-2 was assayed on primary cultures of humanrenal tubular epithelial cells treated with a new specific inhibitor of glucosylceramide synthase (C-9), the ratelimitingfirst step in the glycosphingolipid biosynthetic pathway. The treatment of the cells with 1-5 M C-9 for at least24 h significantly neutralized the action of 1 ng/ml Shiga toxin-2 on cell viability. The expression levels of globotriaosylceramidesignificantly decreased when cells were incubated with 1 M C-9 for 48 h. We propose here that prevention ofglobotriaosyl-ceramide synthesis by the C-9 could be a novel substrate inhibition therapy to neutralize Shiga toxin-2 actionin renal epithelial cells.
publishDate 2008
dc.date.none.fl_str_mv 2008-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/152947
Silberstein, Claudia Marcela; Copeland, Diane P; Chiang, Wei Lien; Repetto, Horacio A.; Ibarra, Cristina Adriana; A glucosylceramide synthase inhibitor prevents the cytotoxic effects of Shiga toxin-2 on human renal tubular epithelial cells; Bentham Science Publishers; Journal of Epithelial Biology and Pharmacology; 1; 12-2008; 71-75
1875-0443
CONICET Digital
CONICET
url http://hdl.handle.net/11336/152947
identifier_str_mv Silberstein, Claudia Marcela; Copeland, Diane P; Chiang, Wei Lien; Repetto, Horacio A.; Ibarra, Cristina Adriana; A glucosylceramide synthase inhibitor prevents the cytotoxic effects of Shiga toxin-2 on human renal tubular epithelial cells; Bentham Science Publishers; Journal of Epithelial Biology and Pharmacology; 1; 12-2008; 71-75
1875-0443
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://benthamopen.com/contents/pdf/JEBP/JEBP-1-71.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.publisher.none.fl_str_mv Bentham Science Publishers
publisher.none.fl_str_mv Bentham Science Publishers
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
_version_ 1842268706100477952
score 13.13397

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