Angiotensin-(1-7) through AT2 receptors mediates tyrosine hydroxylase degradation via the ubiquitin-proteasome pathway

Autores
Lopez Verrilli, María Alejandra; Pirola, Carlos José; Pascual, Mariano Martin; Dominici, Fernando Pablo; Turyn, Daniel; Gironacci, Mariela Mercedes
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hypothalamic norepinephrine (NE) release regulates arterial pressure by altering sympathetic nervous system activity. Because angiotensin (Ang) (1-7) decreases hypothalamic NE release and this effect may be correlated with a diminished NE synthesis, we hypothesize that Ang-(1-7) down-regulates tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamines biosynthesis. We investigated the effect of Ang-(1-7) on centrally TH activity and expression. TH activity was evaluated by the release of tritiated water from (3)H-l-tyrosine. TH expression and phosphorylation were determined by western blot. Hypothalami from normotensive or spontaneously hypertensive rats pre-incubated with Ang-(1-7) showed a significant decrease in TH specific activity. Ang-(1-7) caused a decrease in TH phosphorylation at Ser19 and Ser40 residues. The heptapeptide induced a decrease in TH expression that was blocked by an AT(2) receptor antagonist and not by an AT(1) or Mas receptor antagonist, suggesting the involvement of AT(2) receptors. The proteasome inhibitor MG132 blocked the Ang-(1-7)-mediated TH reduction. In addition, Ang-(1-7) increased the amount of TH-ubiquitin complexes, indicating that the Ang-(1-7)-mediated TH degradation involves ubiquitin conjugation prior to proteasome degradation. We conclude that Ang-(1-7) down-regulates TH activity and expression centrally leading to a decrease in the central NE system activity.
Fil: Lopez Verrilli, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Pascual, Mariano Martin. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Dominici, Fernando Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Turyn, Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Gironacci, Mariela Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Materia
angiotensin-(17)
AT2 receptors
tyrosine hydroxylase
ubiquitinproteasome pathway
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:11336/130456
Acceder
id CONICETDig_cef0327535fffb1dd0357d4a28742c30
oai_identifier_str oai:ri.conicet.gov.ar:11336/130456
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Angiotensin-(1-7) through AT2 receptors mediates tyrosine hydroxylase degradation via the ubiquitin-proteasome pathwayLopez Verrilli, María AlejandraPirola, Carlos JoséPascual, Mariano MartinDominici, Fernando PabloTuryn, DanielGironacci, Mariela Mercedesangiotensin-(17)AT2 receptorstyrosine hydroxylaseubiquitinproteasome pathwayhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Hypothalamic norepinephrine (NE) release regulates arterial pressure by altering sympathetic nervous system activity. Because angiotensin (Ang) (1-7) decreases hypothalamic NE release and this effect may be correlated with a diminished NE synthesis, we hypothesize that Ang-(1-7) down-regulates tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamines biosynthesis. We investigated the effect of Ang-(1-7) on centrally TH activity and expression. TH activity was evaluated by the release of tritiated water from (3)H-l-tyrosine. TH expression and phosphorylation were determined by western blot. Hypothalami from normotensive or spontaneously hypertensive rats pre-incubated with Ang-(1-7) showed a significant decrease in TH specific activity. Ang-(1-7) caused a decrease in TH phosphorylation at Ser19 and Ser40 residues. The heptapeptide induced a decrease in TH expression that was blocked by an AT(2) receptor antagonist and not by an AT(1) or Mas receptor antagonist, suggesting the involvement of AT(2) receptors. The proteasome inhibitor MG132 blocked the Ang-(1-7)-mediated TH reduction. In addition, Ang-(1-7) increased the amount of TH-ubiquitin complexes, indicating that the Ang-(1-7)-mediated TH degradation involves ubiquitin conjugation prior to proteasome degradation. We conclude that Ang-(1-7) down-regulates TH activity and expression centrally leading to a decrease in the central NE system activity.Fil: Lopez Verrilli, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Pascual, Mariano Martin. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dominici, Fernando Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Turyn, Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Gironacci, Mariela Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaWiley Blackwell Publishing, Inc2009-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/130456Lopez Verrilli, María Alejandra; Pirola, Carlos José; Pascual, Mariano Martin; Dominici, Fernando Pablo; Turyn, Daniel; et al.; Angiotensin-(1-7) through AT2 receptors mediates tyrosine hydroxylase degradation via the ubiquitin-proteasome pathway; Wiley Blackwell Publishing, Inc; Journal of Neurochemistry; 109; 2; 1-2009; 326-3350022-3042CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1111/j.1471-4159.2009.05912.xinfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1471-4159.2009.05912.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:14:31Zoai:ri.conicet.gov.ar:11336/130456instacron: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 10:14:31.838CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Angiotensin-(1-7) through AT2 receptors mediates tyrosine hydroxylase degradation via the ubiquitin-proteasome pathway
title Angiotensin-(1-7) through AT2 receptors mediates tyrosine hydroxylase degradation via the ubiquitin-proteasome pathway
spellingShingle Angiotensin-(1-7) through AT2 receptors mediates tyrosine hydroxylase degradation via the ubiquitin-proteasome pathway
Lopez Verrilli, María Alejandra
angiotensin-(17)
AT2 receptors
tyrosine hydroxylase
ubiquitinproteasome pathway
title_short Angiotensin-(1-7) through AT2 receptors mediates tyrosine hydroxylase degradation via the ubiquitin-proteasome pathway
title_full Angiotensin-(1-7) through AT2 receptors mediates tyrosine hydroxylase degradation via the ubiquitin-proteasome pathway
title_fullStr Angiotensin-(1-7) through AT2 receptors mediates tyrosine hydroxylase degradation via the ubiquitin-proteasome pathway
title_full_unstemmed Angiotensin-(1-7) through AT2 receptors mediates tyrosine hydroxylase degradation via the ubiquitin-proteasome pathway
title_sort Angiotensin-(1-7) through AT2 receptors mediates tyrosine hydroxylase degradation via the ubiquitin-proteasome pathway
dc.creator.none.fl_str_mv Lopez Verrilli, María Alejandra
Pirola, Carlos José
Pascual, Mariano Martin
Dominici, Fernando Pablo
Turyn, Daniel
Gironacci, Mariela Mercedes
author Lopez Verrilli, María Alejandra
author_facet Lopez Verrilli, María Alejandra
Pirola, Carlos José
Pascual, Mariano Martin
Dominici, Fernando Pablo
Turyn, Daniel
Gironacci, Mariela Mercedes
author_role author
author2 Pirola, Carlos José
Pascual, Mariano Martin
Dominici, Fernando Pablo
Turyn, Daniel
Gironacci, Mariela Mercedes
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv angiotensin-(17)
AT2 receptors
tyrosine hydroxylase
ubiquitinproteasome pathway
topic angiotensin-(17)
AT2 receptors
tyrosine hydroxylase
ubiquitinproteasome pathway
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Hypothalamic norepinephrine (NE) release regulates arterial pressure by altering sympathetic nervous system activity. Because angiotensin (Ang) (1-7) decreases hypothalamic NE release and this effect may be correlated with a diminished NE synthesis, we hypothesize that Ang-(1-7) down-regulates tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamines biosynthesis. We investigated the effect of Ang-(1-7) on centrally TH activity and expression. TH activity was evaluated by the release of tritiated water from (3)H-l-tyrosine. TH expression and phosphorylation were determined by western blot. Hypothalami from normotensive or spontaneously hypertensive rats pre-incubated with Ang-(1-7) showed a significant decrease in TH specific activity. Ang-(1-7) caused a decrease in TH phosphorylation at Ser19 and Ser40 residues. The heptapeptide induced a decrease in TH expression that was blocked by an AT(2) receptor antagonist and not by an AT(1) or Mas receptor antagonist, suggesting the involvement of AT(2) receptors. The proteasome inhibitor MG132 blocked the Ang-(1-7)-mediated TH reduction. In addition, Ang-(1-7) increased the amount of TH-ubiquitin complexes, indicating that the Ang-(1-7)-mediated TH degradation involves ubiquitin conjugation prior to proteasome degradation. We conclude that Ang-(1-7) down-regulates TH activity and expression centrally leading to a decrease in the central NE system activity.
Fil: Lopez Verrilli, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Pascual, Mariano Martin. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Dominici, Fernando Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Turyn, Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Gironacci, Mariela Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
description Hypothalamic norepinephrine (NE) release regulates arterial pressure by altering sympathetic nervous system activity. Because angiotensin (Ang) (1-7) decreases hypothalamic NE release and this effect may be correlated with a diminished NE synthesis, we hypothesize that Ang-(1-7) down-regulates tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamines biosynthesis. We investigated the effect of Ang-(1-7) on centrally TH activity and expression. TH activity was evaluated by the release of tritiated water from (3)H-l-tyrosine. TH expression and phosphorylation were determined by western blot. Hypothalami from normotensive or spontaneously hypertensive rats pre-incubated with Ang-(1-7) showed a significant decrease in TH specific activity. Ang-(1-7) caused a decrease in TH phosphorylation at Ser19 and Ser40 residues. The heptapeptide induced a decrease in TH expression that was blocked by an AT(2) receptor antagonist and not by an AT(1) or Mas receptor antagonist, suggesting the involvement of AT(2) receptors. The proteasome inhibitor MG132 blocked the Ang-(1-7)-mediated TH reduction. In addition, Ang-(1-7) increased the amount of TH-ubiquitin complexes, indicating that the Ang-(1-7)-mediated TH degradation involves ubiquitin conjugation prior to proteasome degradation. We conclude that Ang-(1-7) down-regulates TH activity and expression centrally leading to a decrease in the central NE system activity.
publishDate 2009
dc.date.none.fl_str_mv 2009-01
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/11336/130456
Lopez Verrilli, María Alejandra; Pirola, Carlos José; Pascual, Mariano Martin; Dominici, Fernando Pablo; Turyn, Daniel; et al.; Angiotensin-(1-7) through AT2 receptors mediates tyrosine hydroxylase degradation via the ubiquitin-proteasome pathway; Wiley Blackwell Publishing, Inc; Journal of Neurochemistry; 109; 2; 1-2009; 326-335
0022-3042
CONICET Digital
CONICET
url http://hdl.handle.net/11336/130456
identifier_str_mv Lopez Verrilli, María Alejandra; Pirola, Carlos José; Pascual, Mariano Martin; Dominici, Fernando Pablo; Turyn, Daniel; et al.; Angiotensin-(1-7) through AT2 receptors mediates tyrosine hydroxylase degradation via the ubiquitin-proteasome pathway; Wiley Blackwell Publishing, Inc; Journal of Neurochemistry; 109; 2; 1-2009; 326-335
0022-3042
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1471-4159.2009.05912.x
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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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