Espermidina diminui a atividade da enzima Na+,K+-ATPase pela via de sinalização NMDA/NOS/GMPc/PKG em hipocampo de ratos
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/11184 |
Resumo: | Spermidine (SPD) is an endogenous polyamine with polycationic structure present in the central nervous system of mammals. SPD regulates biological processes, such as Ca2+ influx by glutamatergic N-methyl-D-aspartate receptor (NMDA receptor), which has been associated with nitric oxide synthase (NOS) and cGMP/PKG pathway activation and a decrease of Na+,K+-ATPase activity in rats cerebral córtex synaptossomes. Decreased Na+,K+-ATPase activity, as well as decreased enzyme expression, directly impairs neurotransmitter signaling with deleterious consequences on learning and memory. The enzyme Na+,K+-ATPase establishes Na+ and K+ gradients across membranes of excitable cells and by this means maintains membrane potential and controls intracellular pH and volume. However, it has not been defined whether SPD modulates Na+,K+-ATPase activity in the hippocampus. In this study we investigated whether SPD alters Na+,K+-ATPase activity in slices of hippocampus from rats, and possible underlying mechanisms. Hippocampal slices and homogenates were incubated with SPD (0.05-10 μM) for 30 minutes. SPD (0.5 and 1 μM) decreased Na+,K+-ATPase activity in slices, but not in homogenates. MK-801 (100 μM), a non-competitive antagonist of NMDA receptor, arcaine (0.5 μM), an antagonist of the polyamine binding site at the NMDA receptor, and L-NAME (100 μM), a nitric oxide synthase inhibitor, prevented the inhibitory effect of SPD (0.5 μM). ODQ (10 μM), a guanylate cyclase inhibitor, and KT5823 (2 μM), a protein kinase G inhibitor, also prevented the inhibitory effect of SPD on Na+,K+-ATPase activity. SPD (0.5 and 1.0 μM) increased NO2 plus NO3 (NOx) levels in slices, MK-801 (100 μM) and arcaine (0.5 μM) prevented the effect of SPD (0.5 μM) on the NOx content. These results suggest that SPD-induced decrease of Na+,K+-ATPase activity involves NMDA/NOS/cGMP/PKG pathway. |
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Espermidina diminui a atividade da enzima Na+,K+-ATPase pela via de sinalização NMDA/NOS/GMPc/PKG em hipocampo de ratosSpermidine inhibited Na+,K+-ATPase activity across NMDA/ NOS/cGMP/PKG pathway signaling in the hippocampus of the ratsEspermidinaNa+,K+-ATPaseReceptor NMDAÓxido NítricoPKGHipocampoNa+,K+-ATPaseNMDA receptorNitric oxideSpermidineHippocampusCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICASpermidine (SPD) is an endogenous polyamine with polycationic structure present in the central nervous system of mammals. SPD regulates biological processes, such as Ca2+ influx by glutamatergic N-methyl-D-aspartate receptor (NMDA receptor), which has been associated with nitric oxide synthase (NOS) and cGMP/PKG pathway activation and a decrease of Na+,K+-ATPase activity in rats cerebral córtex synaptossomes. Decreased Na+,K+-ATPase activity, as well as decreased enzyme expression, directly impairs neurotransmitter signaling with deleterious consequences on learning and memory. The enzyme Na+,K+-ATPase establishes Na+ and K+ gradients across membranes of excitable cells and by this means maintains membrane potential and controls intracellular pH and volume. However, it has not been defined whether SPD modulates Na+,K+-ATPase activity in the hippocampus. In this study we investigated whether SPD alters Na+,K+-ATPase activity in slices of hippocampus from rats, and possible underlying mechanisms. Hippocampal slices and homogenates were incubated with SPD (0.05-10 μM) for 30 minutes. SPD (0.5 and 1 μM) decreased Na+,K+-ATPase activity in slices, but not in homogenates. MK-801 (100 μM), a non-competitive antagonist of NMDA receptor, arcaine (0.5 μM), an antagonist of the polyamine binding site at the NMDA receptor, and L-NAME (100 μM), a nitric oxide synthase inhibitor, prevented the inhibitory effect of SPD (0.5 μM). ODQ (10 μM), a guanylate cyclase inhibitor, and KT5823 (2 μM), a protein kinase G inhibitor, also prevented the inhibitory effect of SPD on Na+,K+-ATPase activity. SPD (0.5 and 1.0 μM) increased NO2 plus NO3 (NOx) levels in slices, MK-801 (100 μM) and arcaine (0.5 μM) prevented the effect of SPD (0.5 μM) on the NOx content. These results suggest that SPD-induced decrease of Na+,K+-ATPase activity involves NMDA/NOS/cGMP/PKG pathway.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorA espermidina (SPD) é uma poliamina endógena com estrutura policatiônica presente no sistema nervoso central (SNC) de mamíferos. A SPD regula muitos processos biológicos, como o influxo de cálcio através dos receptores glutamatérgicos N-metil-D-aspartato (NMDA), o qual tem sido associado com a ativação da enzima óxido nítrico sintase (NOS) e da via de sinalização da guanosina mono fosfato cíclica/proteína quinase dependente de GMPc (GMPc/PKG). Sabe-se que uma diminuição da atividade da Na+,K+-ATPase, bem como a sua expressão, prejudica diretamente a sinalização de neurotransmissores, comprometendo tanto aprendizado e a memória. A enzima Na+,K+-ATPase estabelece os gradientes de Na+ e K+ através da membrana de células excitáveis e desta forma mantém o potencial de membrana e contribui para o controle do volume e do pH celular. No entanto, não está bem definido se a SPD modula a atividade da Na+,K+-ATPase no hipocampo de ratos. Neste estudo foi investigado se SPD altera a atividade da Na+,K+-ATPase em fatias de hipocampo de ratos, e o possível mecanismo envolvido neste processo. As fatias e o homogeneizado de hipocampo foram incubados com SPD (0,05-10 M) por 30 minutos. SPD (0,5 e 1 M) diminuíram a atividade da Na+,K+-ATPase em fatias, mas não no homogeneizado de hipocampo. MK-801 (100 μM), um antagonista não competitivo do receptor NMDA, arcaína (0,5 M), um antagonista do sítio de ligação das poliaminas no receptor NMDA, e L-NAME (100 μM), um inibidor da NOS, preveniram o efeito inibitório da SPD (0,5 M). ODQ (10 μM), um inibidor da enzima guanilato ciclase, e KT5823 (2 μM), um inibidor da proteína quinase dependente de GMPc, também preveniram o efeito inibitório da SPD sobre a atividade da Na+,K+-ATPase. SPD (0,5 e 1,0 μM) aumentaram os níveis de NO2 plus NO3 (NOx) nas fatias de hipocampo. MK-801 (100 μM) e arcaína (0,5 μM) preveniram o efeito da SPD (0,5 μM) sobre conteúdo de NOx. Estes resultados sugerem que a diminuição da atividade da Na+,K+-ATPase induzida pela SPD envolve a via de sinalização NMDA/NOS/GMPc/PKG.Universidade Federal de Santa MariaBRBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaRubin, Maribel Antonellohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794806H7Schetinger, Maria Rosa ChitolinaFurian, Ana Fláviahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705849T6Carvalho, Fabiano Barbosa2012-09-042012-09-042011-12-02info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfCARVALHO, Fabiano Barbosa. SPERMIDINE INHIBITED Na+,K+-ATPase ACTIVITY ACROSS NMDA/ NOS/cGMP/PKG PATHWAY SIGNALING IN THE HIPPOCAMPUS OF THE RATS. 2011. 85 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2011.http://repositorio.ufsm.br/handle/1/11184porinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2022-08-19T15:09:22Zoai:repositorio.ufsm.br:1/11184Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-08-19T15:09:22Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Espermidina diminui a atividade da enzima Na+,K+-ATPase pela via de sinalização NMDA/NOS/GMPc/PKG em hipocampo de ratos Spermidine inhibited Na+,K+-ATPase activity across NMDA/ NOS/cGMP/PKG pathway signaling in the hippocampus of the rats |
title |
Espermidina diminui a atividade da enzima Na+,K+-ATPase pela via de sinalização NMDA/NOS/GMPc/PKG em hipocampo de ratos |
spellingShingle |
Espermidina diminui a atividade da enzima Na+,K+-ATPase pela via de sinalização NMDA/NOS/GMPc/PKG em hipocampo de ratos Carvalho, Fabiano Barbosa Espermidina Na+,K+-ATPase Receptor NMDA Óxido Nítrico PKG Hipocampo Na+,K+-ATPase NMDA receptor Nitric oxide Spermidine Hippocampus CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Espermidina diminui a atividade da enzima Na+,K+-ATPase pela via de sinalização NMDA/NOS/GMPc/PKG em hipocampo de ratos |
title_full |
Espermidina diminui a atividade da enzima Na+,K+-ATPase pela via de sinalização NMDA/NOS/GMPc/PKG em hipocampo de ratos |
title_fullStr |
Espermidina diminui a atividade da enzima Na+,K+-ATPase pela via de sinalização NMDA/NOS/GMPc/PKG em hipocampo de ratos |
title_full_unstemmed |
Espermidina diminui a atividade da enzima Na+,K+-ATPase pela via de sinalização NMDA/NOS/GMPc/PKG em hipocampo de ratos |
title_sort |
Espermidina diminui a atividade da enzima Na+,K+-ATPase pela via de sinalização NMDA/NOS/GMPc/PKG em hipocampo de ratos |
author |
Carvalho, Fabiano Barbosa |
author_facet |
Carvalho, Fabiano Barbosa |
author_role |
author |
dc.contributor.none.fl_str_mv |
Rubin, Maribel Antonello http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794806H7 Schetinger, Maria Rosa Chitolina Furian, Ana Flávia http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705849T6 |
dc.contributor.author.fl_str_mv |
Carvalho, Fabiano Barbosa |
dc.subject.por.fl_str_mv |
Espermidina Na+,K+-ATPase Receptor NMDA Óxido Nítrico PKG Hipocampo Na+,K+-ATPase NMDA receptor Nitric oxide Spermidine Hippocampus CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
Espermidina Na+,K+-ATPase Receptor NMDA Óxido Nítrico PKG Hipocampo Na+,K+-ATPase NMDA receptor Nitric oxide Spermidine Hippocampus CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Spermidine (SPD) is an endogenous polyamine with polycationic structure present in the central nervous system of mammals. SPD regulates biological processes, such as Ca2+ influx by glutamatergic N-methyl-D-aspartate receptor (NMDA receptor), which has been associated with nitric oxide synthase (NOS) and cGMP/PKG pathway activation and a decrease of Na+,K+-ATPase activity in rats cerebral córtex synaptossomes. Decreased Na+,K+-ATPase activity, as well as decreased enzyme expression, directly impairs neurotransmitter signaling with deleterious consequences on learning and memory. The enzyme Na+,K+-ATPase establishes Na+ and K+ gradients across membranes of excitable cells and by this means maintains membrane potential and controls intracellular pH and volume. However, it has not been defined whether SPD modulates Na+,K+-ATPase activity in the hippocampus. In this study we investigated whether SPD alters Na+,K+-ATPase activity in slices of hippocampus from rats, and possible underlying mechanisms. Hippocampal slices and homogenates were incubated with SPD (0.05-10 μM) for 30 minutes. SPD (0.5 and 1 μM) decreased Na+,K+-ATPase activity in slices, but not in homogenates. MK-801 (100 μM), a non-competitive antagonist of NMDA receptor, arcaine (0.5 μM), an antagonist of the polyamine binding site at the NMDA receptor, and L-NAME (100 μM), a nitric oxide synthase inhibitor, prevented the inhibitory effect of SPD (0.5 μM). ODQ (10 μM), a guanylate cyclase inhibitor, and KT5823 (2 μM), a protein kinase G inhibitor, also prevented the inhibitory effect of SPD on Na+,K+-ATPase activity. SPD (0.5 and 1.0 μM) increased NO2 plus NO3 (NOx) levels in slices, MK-801 (100 μM) and arcaine (0.5 μM) prevented the effect of SPD (0.5 μM) on the NOx content. These results suggest that SPD-induced decrease of Na+,K+-ATPase activity involves NMDA/NOS/cGMP/PKG pathway. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-12-02 2012-09-04 2012-09-04 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
CARVALHO, Fabiano Barbosa. SPERMIDINE INHIBITED Na+,K+-ATPase ACTIVITY ACROSS NMDA/ NOS/cGMP/PKG PATHWAY SIGNALING IN THE HIPPOCAMPUS OF THE RATS. 2011. 85 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2011. http://repositorio.ufsm.br/handle/1/11184 |
identifier_str_mv |
CARVALHO, Fabiano Barbosa. SPERMIDINE INHIBITED Na+,K+-ATPase ACTIVITY ACROSS NMDA/ NOS/cGMP/PKG PATHWAY SIGNALING IN THE HIPPOCAMPUS OF THE RATS. 2011. 85 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2011. |
url |
http://repositorio.ufsm.br/handle/1/11184 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1805922045598367744 |