Signaling cascade of insulin-induced stimulation of L-dopa uptake in renal proximal tubule cells

Autores
Carranza, Maria Andrea; Musolino, Patricia L.; Villar, Marcelo Jose; Nowicki, Susana
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The inward L-dihydroxyphenylalanine (L-dopa) transport supplies renal proximal tubule cells (PTCs) with the precursor for dopamine synthesis. We have previously described insulin-induced stimulation of L-dopa uptake into PTCs. In the present paper we examined insulinrelated signaling pathways involved in the increase of L-dopa transport into isolated rat PTCs. Insulin (50?500 U/ml) increased L-dopa uptake by PTCs, reaching the maximal increment (60% over the control) at 200 U/ml. At this concentration, insulin also increased insulin receptor tyrosine phosphorylation. Both effects were abrogated by the tyrosine kinase inhibitor genistein (5 M). In line, inhibition of the protein tyrosine phosphatase by pervanadate (0.2?100 M) caused a concentration-dependent increase in both the uptake of L-dopa (up to 400%) and protein tyrosine phosphorylation. A synergistic effect between pervanadate and insulin on L-dopa uptake was observed only when threshold (0.2 M), but not maximal (5 M), concentrations of pervanadate were assayed. Insulin-induced stimulation of L-dopa uptake was also abolished by inhibition of phosphatidylinositol 3-kinase (PI3K; 100 nM wortmannin, and 25 M LY-294002) and protein kinase C (PKC; 1 M RO-318220). Insulin-induced activation of PKC- was confirmed in vitro by its translocation from the cytosol to the membrane fraction, and in vivo by immunohistochemistry studies. Insulin caused a wortmannin-sensitive increase in Akt/protein kinase B (Akt/PKB) phosphorylation and a dose-dependent translocation of Akt/PKB to the membrane fraction. Our findings suggest that insulin activates PKC- , and Akt/PKB downstream of PI3K, and that these pathways contribute to the insulin-induced increase of L-dopa uptake into PTCs.
Fil: Carranza, Maria Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Musolino, Patricia L.. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Villar, Marcelo Jose. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Nowicki, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Materia
RENAL DOPAMINE
INSULIN SIGNALING
LEVO DOPA
KIDNEY
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:11336/160571
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/160571
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Signaling cascade of insulin-induced stimulation of L-dopa uptake in renal proximal tubule cellsCarranza, Maria AndreaMusolino, Patricia L.Villar, Marcelo JoseNowicki, SusanaRENAL DOPAMINEINSULIN SIGNALINGLEVO DOPAKIDNEYhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The inward L-dihydroxyphenylalanine (L-dopa) transport supplies renal proximal tubule cells (PTCs) with the precursor for dopamine synthesis. We have previously described insulin-induced stimulation of L-dopa uptake into PTCs. In the present paper we examined insulinrelated signaling pathways involved in the increase of L-dopa transport into isolated rat PTCs. Insulin (50?500 U/ml) increased L-dopa uptake by PTCs, reaching the maximal increment (60% over the control) at 200 U/ml. At this concentration, insulin also increased insulin receptor tyrosine phosphorylation. Both effects were abrogated by the tyrosine kinase inhibitor genistein (5 M). In line, inhibition of the protein tyrosine phosphatase by pervanadate (0.2?100 M) caused a concentration-dependent increase in both the uptake of L-dopa (up to 400%) and protein tyrosine phosphorylation. A synergistic effect between pervanadate and insulin on L-dopa uptake was observed only when threshold (0.2 M), but not maximal (5 M), concentrations of pervanadate were assayed. Insulin-induced stimulation of L-dopa uptake was also abolished by inhibition of phosphatidylinositol 3-kinase (PI3K; 100 nM wortmannin, and 25 M LY-294002) and protein kinase C (PKC; 1 M RO-318220). Insulin-induced activation of PKC- was confirmed in vitro by its translocation from the cytosol to the membrane fraction, and in vivo by immunohistochemistry studies. Insulin caused a wortmannin-sensitive increase in Akt/protein kinase B (Akt/PKB) phosphorylation and a dose-dependent translocation of Akt/PKB to the membrane fraction. Our findings suggest that insulin activates PKC- , and Akt/PKB downstream of PI3K, and that these pathways contribute to the insulin-induced increase of L-dopa uptake into PTCs.Fil: Carranza, Maria Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Musolino, Patricia L.. Universidad Austral. Facultad de Ciencias Biomédicas; ArgentinaFil: Villar, Marcelo Jose. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nowicki, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaAmerican Physiological Society2008-12info: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/11336/160571Carranza, Maria Andrea; Musolino, Patricia L.; Villar, Marcelo Jose; Nowicki, Susana; Signaling cascade of insulin-induced stimulation of L-dopa uptake in renal proximal tubule cells; American Physiological Society; American Journal of Physiology-cell Physiology; 295; 6; 12-2008; 1602-16090363-6143CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1152/ajpcell.00090.2008info:eu-repo/semantics/altIdentifier/url/https://pubmed.ncbi.nlm.nih.gov/18842830/info:eu-repo/semantics/altIdentifier/url/https://journals.physiology.org/doi/full/10.1152/ajpcell.00090.2008?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.orginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:48:12Zoai:ri.conicet.gov.ar:11336/160571instacron: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 09:48:12.436CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Signaling cascade of insulin-induced stimulation of L-dopa uptake in renal proximal tubule cells
title Signaling cascade of insulin-induced stimulation of L-dopa uptake in renal proximal tubule cells
spellingShingle Signaling cascade of insulin-induced stimulation of L-dopa uptake in renal proximal tubule cells
Carranza, Maria Andrea
RENAL DOPAMINE
INSULIN SIGNALING
LEVO DOPA
KIDNEY
title_short Signaling cascade of insulin-induced stimulation of L-dopa uptake in renal proximal tubule cells
title_full Signaling cascade of insulin-induced stimulation of L-dopa uptake in renal proximal tubule cells
title_fullStr Signaling cascade of insulin-induced stimulation of L-dopa uptake in renal proximal tubule cells
title_full_unstemmed Signaling cascade of insulin-induced stimulation of L-dopa uptake in renal proximal tubule cells
title_sort Signaling cascade of insulin-induced stimulation of L-dopa uptake in renal proximal tubule cells
dc.creator.none.fl_str_mv Carranza, Maria Andrea
Musolino, Patricia L.
Villar, Marcelo Jose
Nowicki, Susana
author Carranza, Maria Andrea
author_facet Carranza, Maria Andrea
Musolino, Patricia L.
Villar, Marcelo Jose
Nowicki, Susana
author_role author
author2 Musolino, Patricia L.
Villar, Marcelo Jose
Nowicki, Susana
author2_role author
author
author
dc.subject.none.fl_str_mv RENAL DOPAMINE
INSULIN SIGNALING
LEVO DOPA
KIDNEY
topic RENAL DOPAMINE
INSULIN SIGNALING
LEVO DOPA
KIDNEY
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The inward L-dihydroxyphenylalanine (L-dopa) transport supplies renal proximal tubule cells (PTCs) with the precursor for dopamine synthesis. We have previously described insulin-induced stimulation of L-dopa uptake into PTCs. In the present paper we examined insulinrelated signaling pathways involved in the increase of L-dopa transport into isolated rat PTCs. Insulin (50?500 U/ml) increased L-dopa uptake by PTCs, reaching the maximal increment (60% over the control) at 200 U/ml. At this concentration, insulin also increased insulin receptor tyrosine phosphorylation. Both effects were abrogated by the tyrosine kinase inhibitor genistein (5 M). In line, inhibition of the protein tyrosine phosphatase by pervanadate (0.2?100 M) caused a concentration-dependent increase in both the uptake of L-dopa (up to 400%) and protein tyrosine phosphorylation. A synergistic effect between pervanadate and insulin on L-dopa uptake was observed only when threshold (0.2 M), but not maximal (5 M), concentrations of pervanadate were assayed. Insulin-induced stimulation of L-dopa uptake was also abolished by inhibition of phosphatidylinositol 3-kinase (PI3K; 100 nM wortmannin, and 25 M LY-294002) and protein kinase C (PKC; 1 M RO-318220). Insulin-induced activation of PKC- was confirmed in vitro by its translocation from the cytosol to the membrane fraction, and in vivo by immunohistochemistry studies. Insulin caused a wortmannin-sensitive increase in Akt/protein kinase B (Akt/PKB) phosphorylation and a dose-dependent translocation of Akt/PKB to the membrane fraction. Our findings suggest that insulin activates PKC- , and Akt/PKB downstream of PI3K, and that these pathways contribute to the insulin-induced increase of L-dopa uptake into PTCs.
Fil: Carranza, Maria Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Musolino, Patricia L.. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Villar, Marcelo Jose. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Nowicki, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
description The inward L-dihydroxyphenylalanine (L-dopa) transport supplies renal proximal tubule cells (PTCs) with the precursor for dopamine synthesis. We have previously described insulin-induced stimulation of L-dopa uptake into PTCs. In the present paper we examined insulinrelated signaling pathways involved in the increase of L-dopa transport into isolated rat PTCs. Insulin (50?500 U/ml) increased L-dopa uptake by PTCs, reaching the maximal increment (60% over the control) at 200 U/ml. At this concentration, insulin also increased insulin receptor tyrosine phosphorylation. Both effects were abrogated by the tyrosine kinase inhibitor genistein (5 M). In line, inhibition of the protein tyrosine phosphatase by pervanadate (0.2?100 M) caused a concentration-dependent increase in both the uptake of L-dopa (up to 400%) and protein tyrosine phosphorylation. A synergistic effect between pervanadate and insulin on L-dopa uptake was observed only when threshold (0.2 M), but not maximal (5 M), concentrations of pervanadate were assayed. Insulin-induced stimulation of L-dopa uptake was also abolished by inhibition of phosphatidylinositol 3-kinase (PI3K; 100 nM wortmannin, and 25 M LY-294002) and protein kinase C (PKC; 1 M RO-318220). Insulin-induced activation of PKC- was confirmed in vitro by its translocation from the cytosol to the membrane fraction, and in vivo by immunohistochemistry studies. Insulin caused a wortmannin-sensitive increase in Akt/protein kinase B (Akt/PKB) phosphorylation and a dose-dependent translocation of Akt/PKB to the membrane fraction. Our findings suggest that insulin activates PKC- , and Akt/PKB downstream of PI3K, and that these pathways contribute to the insulin-induced increase of L-dopa uptake into PTCs.
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/11336/160571
Carranza, Maria Andrea; Musolino, Patricia L.; Villar, Marcelo Jose; Nowicki, Susana; Signaling cascade of insulin-induced stimulation of L-dopa uptake in renal proximal tubule cells; American Physiological Society; American Journal of Physiology-cell Physiology; 295; 6; 12-2008; 1602-1609
0363-6143
CONICET Digital
CONICET
url http://hdl.handle.net/11336/160571
identifier_str_mv Carranza, Maria Andrea; Musolino, Patricia L.; Villar, Marcelo Jose; Nowicki, Susana; Signaling cascade of insulin-induced stimulation of L-dopa uptake in renal proximal tubule cells; American Physiological Society; American Journal of Physiology-cell Physiology; 295; 6; 12-2008; 1602-1609
0363-6143
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpcell.00090.2008
info:eu-repo/semantics/altIdentifier/url/https://pubmed.ncbi.nlm.nih.gov/18842830/
info:eu-repo/semantics/altIdentifier/url/https://journals.physiology.org/doi/full/10.1152/ajpcell.00090.2008?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org
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 American Physiological Society
publisher.none.fl_str_mv American Physiological Society
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 13.13397

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