Exposure of luminal membranes of LLC-PK1 cells to ANG II induces dimerization of AT(1)/AT(2) receptors to activate SERCA and to promote Ca2+ mobilization
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/34733 http://dx.doi.org/10.1152/ajprenal.00381.2011 |
Resumo: | Ferrao FM, Lara LS, Axelband F, Dias J, Carmona AK, Reis RI, Costa-Neto CM, Vieyra A, Lowe J. Exposure of luminal membranes of LLC-PK1 cells to ANG II induces dimerization of AT(1)/AT(2) receptors to activate SERCA and to promote Ca2+ mobilization. Am J Physiol Renal Physiol 302: F875-F883, 2012. First published January 4, 2012; doi:10.1152/ajprenal.00381.2011.-ANG II is secreted into the lumens of proximal tubules where it is also synthesized, thus increasing the local concentration of the peptide to levels of potential physiological relevance. in the present work, we studied the effect of ANG II via the luminal membranes of LLC-PK1 cells on Ca2+-ATPase of the sarco(endo) plasmic reticulum (SERCA) and plasma membrane (PMCA). ANG II (at concentrations found in the lumen) stimulated rapid (30 s) and persistent (30 min) SERCA activity by more than 100% and increased Ca2+ mobilization. Pretreatment with ANG II for 30 min enhanced the ANG II-induced Ca2+ spark, demonstrating a positively self-sustained stimulus of Ca2+ mobilization by ANG II. ANG II in the medium facing the luminal side of the cells decreased with time with no formation of metabolites, indicating peptide internalization. ANG II increased heterodimerization of AT(1) and AT(2) receptors by 140%, and either losartan or PD123319 completely blocked the stimulation of SERCA by ANG II. Using the PLC inhibitor U73122, PMA, and calphostin C, it was possible to demonstrate the involvement of a PLC -> DAG(PMA)-> PKC pathway in the stimulation of SERCA by ANG II with no effect on PMCA. We conclude that ANG II triggers SERCA activation via the luminal membrane, increasing the Ca2+ stock in the reticulum to ensure a more efficient subsequent mobilization of Ca2+. This first report on the regulation of SERCA activity by ANG II shows a new mechanism for Ca2+ homeostasis in renal cells and also for regulation of Ca2+-modulated fluid reabsorption in proximal tubules. |
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Ferrao, Fernanda M.Lara, Lucienne S.Axelband, FlaviaDias, JulianaCarmona, Adriana K. [UNIFESP]Reis, Rosana I.Costa-Neto, Claudio M.Vieyra, AdalbertoLowe, JenniferUniversidade Federal do Rio de Janeiro (UFRJ)Inst Nacl Ciencia & Tecnol Biol Estrutural & BioiUniversidade Federal de São Paulo (UNIFESP)Universidade de São Paulo (USP)2016-01-24T14:27:00Z2016-01-24T14:27:00Z2012-04-01American Journal of Physiology-renal Physiology. Bethesda: Amer Physiological Soc, v. 302, n. 7, p. F875-F883, 2012.1931-857Xhttp://repositorio.unifesp.br/handle/11600/34733http://dx.doi.org/10.1152/ajprenal.00381.201110.1152/ajprenal.00381.2011WOS:000302339500009Ferrao FM, Lara LS, Axelband F, Dias J, Carmona AK, Reis RI, Costa-Neto CM, Vieyra A, Lowe J. Exposure of luminal membranes of LLC-PK1 cells to ANG II induces dimerization of AT(1)/AT(2) receptors to activate SERCA and to promote Ca2+ mobilization. Am J Physiol Renal Physiol 302: F875-F883, 2012. First published January 4, 2012; doi:10.1152/ajprenal.00381.2011.-ANG II is secreted into the lumens of proximal tubules where it is also synthesized, thus increasing the local concentration of the peptide to levels of potential physiological relevance. in the present work, we studied the effect of ANG II via the luminal membranes of LLC-PK1 cells on Ca2+-ATPase of the sarco(endo) plasmic reticulum (SERCA) and plasma membrane (PMCA). ANG II (at concentrations found in the lumen) stimulated rapid (30 s) and persistent (30 min) SERCA activity by more than 100% and increased Ca2+ mobilization. Pretreatment with ANG II for 30 min enhanced the ANG II-induced Ca2+ spark, demonstrating a positively self-sustained stimulus of Ca2+ mobilization by ANG II. ANG II in the medium facing the luminal side of the cells decreased with time with no formation of metabolites, indicating peptide internalization. ANG II increased heterodimerization of AT(1) and AT(2) receptors by 140%, and either losartan or PD123319 completely blocked the stimulation of SERCA by ANG II. Using the PLC inhibitor U73122, PMA, and calphostin C, it was possible to demonstrate the involvement of a PLC -> DAG(PMA)-> PKC pathway in the stimulation of SERCA by ANG II with no effect on PMCA. We conclude that ANG II triggers SERCA activation via the luminal membrane, increasing the Ca2+ stock in the reticulum to ensure a more efficient subsequent mobilization of Ca2+. This first report on the regulation of SERCA activity by ANG II shows a new mechanism for Ca2+ homeostasis in renal cells and also for regulation of Ca2+-modulated fluid reabsorption in proximal tubules.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Fis Quim Biol Aida Hasson Voloch, BR-21941902 Rio de Janeiro, BrazilInst Nacl Ciencia & Tecnol Biol Estrutural & Bioi, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilUniv Fed Rio de Janeiro, Inst Ciencias Biomed, BR-21941902 Rio de Janeiro, BrazilUniv São Paulo, Dept Biochem & Immunol, Sch Med Ribeirao Preto, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilWeb of ScienceF875-F883engAmer Physiological SocAmerican Journal of Physiology-renal Physiologyluminal effect of ANG IICa2+ sparksproximal tubule Ca2+ homeostasisfluid reabsorptionExposure of luminal membranes of LLC-PK1 cells to ANG II induces dimerization of AT(1)/AT(2) receptors to activate SERCA and to promote Ca2+ mobilizationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/347332023-02-15 09:10:17.87metadata only accessoai:repositorio.unifesp.br:11600/34733Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-02-15T12:10:17Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Exposure of luminal membranes of LLC-PK1 cells to ANG II induces dimerization of AT(1)/AT(2) receptors to activate SERCA and to promote Ca2+ mobilization |
title |
Exposure of luminal membranes of LLC-PK1 cells to ANG II induces dimerization of AT(1)/AT(2) receptors to activate SERCA and to promote Ca2+ mobilization |
spellingShingle |
Exposure of luminal membranes of LLC-PK1 cells to ANG II induces dimerization of AT(1)/AT(2) receptors to activate SERCA and to promote Ca2+ mobilization Ferrao, Fernanda M. luminal effect of ANG II Ca2+ sparks proximal tubule Ca2+ homeostasis fluid reabsorption |
title_short |
Exposure of luminal membranes of LLC-PK1 cells to ANG II induces dimerization of AT(1)/AT(2) receptors to activate SERCA and to promote Ca2+ mobilization |
title_full |
Exposure of luminal membranes of LLC-PK1 cells to ANG II induces dimerization of AT(1)/AT(2) receptors to activate SERCA and to promote Ca2+ mobilization |
title_fullStr |
Exposure of luminal membranes of LLC-PK1 cells to ANG II induces dimerization of AT(1)/AT(2) receptors to activate SERCA and to promote Ca2+ mobilization |
title_full_unstemmed |
Exposure of luminal membranes of LLC-PK1 cells to ANG II induces dimerization of AT(1)/AT(2) receptors to activate SERCA and to promote Ca2+ mobilization |
title_sort |
Exposure of luminal membranes of LLC-PK1 cells to ANG II induces dimerization of AT(1)/AT(2) receptors to activate SERCA and to promote Ca2+ mobilization |
author |
Ferrao, Fernanda M. |
author_facet |
Ferrao, Fernanda M. Lara, Lucienne S. Axelband, Flavia Dias, Juliana Carmona, Adriana K. [UNIFESP] Reis, Rosana I. Costa-Neto, Claudio M. Vieyra, Adalberto Lowe, Jennifer |
author_role |
author |
author2 |
Lara, Lucienne S. Axelband, Flavia Dias, Juliana Carmona, Adriana K. [UNIFESP] Reis, Rosana I. Costa-Neto, Claudio M. Vieyra, Adalberto Lowe, Jennifer |
author2_role |
author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal do Rio de Janeiro (UFRJ) Inst Nacl Ciencia & Tecnol Biol Estrutural & Bioi Universidade Federal de São Paulo (UNIFESP) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Ferrao, Fernanda M. Lara, Lucienne S. Axelband, Flavia Dias, Juliana Carmona, Adriana K. [UNIFESP] Reis, Rosana I. Costa-Neto, Claudio M. Vieyra, Adalberto Lowe, Jennifer |
dc.subject.eng.fl_str_mv |
luminal effect of ANG II Ca2+ sparks proximal tubule Ca2+ homeostasis fluid reabsorption |
topic |
luminal effect of ANG II Ca2+ sparks proximal tubule Ca2+ homeostasis fluid reabsorption |
description |
Ferrao FM, Lara LS, Axelband F, Dias J, Carmona AK, Reis RI, Costa-Neto CM, Vieyra A, Lowe J. Exposure of luminal membranes of LLC-PK1 cells to ANG II induces dimerization of AT(1)/AT(2) receptors to activate SERCA and to promote Ca2+ mobilization. Am J Physiol Renal Physiol 302: F875-F883, 2012. First published January 4, 2012; doi:10.1152/ajprenal.00381.2011.-ANG II is secreted into the lumens of proximal tubules where it is also synthesized, thus increasing the local concentration of the peptide to levels of potential physiological relevance. in the present work, we studied the effect of ANG II via the luminal membranes of LLC-PK1 cells on Ca2+-ATPase of the sarco(endo) plasmic reticulum (SERCA) and plasma membrane (PMCA). ANG II (at concentrations found in the lumen) stimulated rapid (30 s) and persistent (30 min) SERCA activity by more than 100% and increased Ca2+ mobilization. Pretreatment with ANG II for 30 min enhanced the ANG II-induced Ca2+ spark, demonstrating a positively self-sustained stimulus of Ca2+ mobilization by ANG II. ANG II in the medium facing the luminal side of the cells decreased with time with no formation of metabolites, indicating peptide internalization. ANG II increased heterodimerization of AT(1) and AT(2) receptors by 140%, and either losartan or PD123319 completely blocked the stimulation of SERCA by ANG II. Using the PLC inhibitor U73122, PMA, and calphostin C, it was possible to demonstrate the involvement of a PLC -> DAG(PMA)-> PKC pathway in the stimulation of SERCA by ANG II with no effect on PMCA. We conclude that ANG II triggers SERCA activation via the luminal membrane, increasing the Ca2+ stock in the reticulum to ensure a more efficient subsequent mobilization of Ca2+. This first report on the regulation of SERCA activity by ANG II shows a new mechanism for Ca2+ homeostasis in renal cells and also for regulation of Ca2+-modulated fluid reabsorption in proximal tubules. |
publishDate |
2012 |
dc.date.issued.fl_str_mv |
2012-04-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:27:00Z |
dc.date.available.fl_str_mv |
2016-01-24T14:27:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
American Journal of Physiology-renal Physiology. Bethesda: Amer Physiological Soc, v. 302, n. 7, p. F875-F883, 2012. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/34733 http://dx.doi.org/10.1152/ajprenal.00381.2011 |
dc.identifier.issn.none.fl_str_mv |
1931-857X |
dc.identifier.doi.none.fl_str_mv |
10.1152/ajprenal.00381.2011 |
dc.identifier.wos.none.fl_str_mv |
WOS:000302339500009 |
identifier_str_mv |
American Journal of Physiology-renal Physiology. Bethesda: Amer Physiological Soc, v. 302, n. 7, p. F875-F883, 2012. 1931-857X 10.1152/ajprenal.00381.2011 WOS:000302339500009 |
url |
http://repositorio.unifesp.br/handle/11600/34733 http://dx.doi.org/10.1152/ajprenal.00381.2011 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
American Journal of Physiology-renal Physiology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
F875-F883 |
dc.publisher.none.fl_str_mv |
Amer Physiological Soc |
publisher.none.fl_str_mv |
Amer Physiological Soc |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1802764191294029824 |