Alpha-ketoisocaproic acid increases phosphorylation of intermediate filament proteins from rat cerebral cortex by mechanisms involving Ca²+ an cAMP
Autor(a) principal: | |
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Data de Publicação: | 2005 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/218302 |
Resumo: | We have previously described that a-ketoisocaproic acid (KIC), the main metabolite accumulating in maple syrup urine disease (MSUD), increased the in vitro phosphorylation of cytoskeletal proteins in cerebral cortex of 17- and 21-day-old rats through NMDA glutamatergic receptors. In the present study we investigated the protein kinases involved in the effects of KIC on the phosphorylating system associated with the cytoskeletal fraction and provided an insight on the mechanisms involved in such effects. Results showed that 1 mM KIC increased the in vitro incorporation of 32P into intermediate filament (IF) proteins in slices of 21-day-old rats at shorter incubation times (5 min) than previously reported. Furthermore, this effect was prevented by 10 lM KN-93 and 10 lM H-89, indicating that KIC treatment increased Ca2+/calmodulin- (PKCaMII) and cAMP- (PKA) dependent protein kinases activities, respectively. Nifedipine (100 lM), a blocker of voltage-dependent calcium channels (VDCC), DL-AP5 (100 lM), a NMDA glutamate receptor antagonist and BAPTA-AM (50 lM), a potent intracellular Ca2+ chelator, were also able to prevent KICinduced increase of in vitro phosphorylation of IF proteins. In addition, KIC treatment was able to significantly increase the intracellular cAMP levels. This data support the view that KIC increased the activity of the second messenger-dependent protein kinases PKCaMII and PKA through intracellular Ca2+ levels. Considering that hyperphosphorylation of cytoskeletal proteins is related to neurodegeneration it is presumed that the Ca2+-dependent hyperphosphorylation of IF proteins caused by KIC may be involved to the neuropathology of MSUD patients. |
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Funchal, Cláudia da SilvaZamoner, ArianeQuincozes-Santos, AndréLoureiro, Samanta OliveiraPureur, Regina PessoaWajner, Moacir2021-03-02T04:15:44Z20050364-3190http://hdl.handle.net/10183/218302000527184We have previously described that a-ketoisocaproic acid (KIC), the main metabolite accumulating in maple syrup urine disease (MSUD), increased the in vitro phosphorylation of cytoskeletal proteins in cerebral cortex of 17- and 21-day-old rats through NMDA glutamatergic receptors. In the present study we investigated the protein kinases involved in the effects of KIC on the phosphorylating system associated with the cytoskeletal fraction and provided an insight on the mechanisms involved in such effects. Results showed that 1 mM KIC increased the in vitro incorporation of 32P into intermediate filament (IF) proteins in slices of 21-day-old rats at shorter incubation times (5 min) than previously reported. Furthermore, this effect was prevented by 10 lM KN-93 and 10 lM H-89, indicating that KIC treatment increased Ca2+/calmodulin- (PKCaMII) and cAMP- (PKA) dependent protein kinases activities, respectively. Nifedipine (100 lM), a blocker of voltage-dependent calcium channels (VDCC), DL-AP5 (100 lM), a NMDA glutamate receptor antagonist and BAPTA-AM (50 lM), a potent intracellular Ca2+ chelator, were also able to prevent KICinduced increase of in vitro phosphorylation of IF proteins. In addition, KIC treatment was able to significantly increase the intracellular cAMP levels. This data support the view that KIC increased the activity of the second messenger-dependent protein kinases PKCaMII and PKA through intracellular Ca2+ levels. Considering that hyperphosphorylation of cytoskeletal proteins is related to neurodegeneration it is presumed that the Ca2+-dependent hyperphosphorylation of IF proteins caused by KIC may be involved to the neuropathology of MSUD patients.application/pdfengNeurochemical research. New York, NY. Vol. 30, no. 9 ( 2005), p. 1139-1146Filamentos intermediáriosDoença da urina de xarope de bordoFosforilaçãoα-Ketoisocaproic acidCalciumcAMPIntermediate filamentsMaple syrup urine diseasePhosphorylationAlpha-ketoisocaproic acid increases phosphorylation of intermediate filament proteins from rat cerebral cortex by mechanisms involving Ca²+ an cAMPEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT000527184.pdf.txt000527184.pdf.txtExtracted Texttext/plain0http://www.lume.ufrgs.br/bitstream/10183/218302/2/000527184.pdf.txtd41d8cd98f00b204e9800998ecf8427eMD52ORIGINAL000527184.pdfTexto completo (inglês)application/pdf3117203http://www.lume.ufrgs.br/bitstream/10183/218302/1/000527184.pdfb247c99acb3db16009fe95dc5d5df32eMD5110183/2183022021-04-12 08:33:24.731533oai:www.lume.ufrgs.br:10183/218302Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2021-04-12T11:33:24Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Alpha-ketoisocaproic acid increases phosphorylation of intermediate filament proteins from rat cerebral cortex by mechanisms involving Ca²+ an cAMP |
title |
Alpha-ketoisocaproic acid increases phosphorylation of intermediate filament proteins from rat cerebral cortex by mechanisms involving Ca²+ an cAMP |
spellingShingle |
Alpha-ketoisocaproic acid increases phosphorylation of intermediate filament proteins from rat cerebral cortex by mechanisms involving Ca²+ an cAMP Funchal, Cláudia da Silva Filamentos intermediários Doença da urina de xarope de bordo Fosforilação α-Ketoisocaproic acid Calcium cAMP Intermediate filaments Maple syrup urine disease Phosphorylation |
title_short |
Alpha-ketoisocaproic acid increases phosphorylation of intermediate filament proteins from rat cerebral cortex by mechanisms involving Ca²+ an cAMP |
title_full |
Alpha-ketoisocaproic acid increases phosphorylation of intermediate filament proteins from rat cerebral cortex by mechanisms involving Ca²+ an cAMP |
title_fullStr |
Alpha-ketoisocaproic acid increases phosphorylation of intermediate filament proteins from rat cerebral cortex by mechanisms involving Ca²+ an cAMP |
title_full_unstemmed |
Alpha-ketoisocaproic acid increases phosphorylation of intermediate filament proteins from rat cerebral cortex by mechanisms involving Ca²+ an cAMP |
title_sort |
Alpha-ketoisocaproic acid increases phosphorylation of intermediate filament proteins from rat cerebral cortex by mechanisms involving Ca²+ an cAMP |
author |
Funchal, Cláudia da Silva |
author_facet |
Funchal, Cláudia da Silva Zamoner, Ariane Quincozes-Santos, André Loureiro, Samanta Oliveira Pureur, Regina Pessoa Wajner, Moacir |
author_role |
author |
author2 |
Zamoner, Ariane Quincozes-Santos, André Loureiro, Samanta Oliveira Pureur, Regina Pessoa Wajner, Moacir |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Funchal, Cláudia da Silva Zamoner, Ariane Quincozes-Santos, André Loureiro, Samanta Oliveira Pureur, Regina Pessoa Wajner, Moacir |
dc.subject.por.fl_str_mv |
Filamentos intermediários Doença da urina de xarope de bordo Fosforilação |
topic |
Filamentos intermediários Doença da urina de xarope de bordo Fosforilação α-Ketoisocaproic acid Calcium cAMP Intermediate filaments Maple syrup urine disease Phosphorylation |
dc.subject.eng.fl_str_mv |
α-Ketoisocaproic acid Calcium cAMP Intermediate filaments Maple syrup urine disease Phosphorylation |
description |
We have previously described that a-ketoisocaproic acid (KIC), the main metabolite accumulating in maple syrup urine disease (MSUD), increased the in vitro phosphorylation of cytoskeletal proteins in cerebral cortex of 17- and 21-day-old rats through NMDA glutamatergic receptors. In the present study we investigated the protein kinases involved in the effects of KIC on the phosphorylating system associated with the cytoskeletal fraction and provided an insight on the mechanisms involved in such effects. Results showed that 1 mM KIC increased the in vitro incorporation of 32P into intermediate filament (IF) proteins in slices of 21-day-old rats at shorter incubation times (5 min) than previously reported. Furthermore, this effect was prevented by 10 lM KN-93 and 10 lM H-89, indicating that KIC treatment increased Ca2+/calmodulin- (PKCaMII) and cAMP- (PKA) dependent protein kinases activities, respectively. Nifedipine (100 lM), a blocker of voltage-dependent calcium channels (VDCC), DL-AP5 (100 lM), a NMDA glutamate receptor antagonist and BAPTA-AM (50 lM), a potent intracellular Ca2+ chelator, were also able to prevent KICinduced increase of in vitro phosphorylation of IF proteins. In addition, KIC treatment was able to significantly increase the intracellular cAMP levels. This data support the view that KIC increased the activity of the second messenger-dependent protein kinases PKCaMII and PKA through intracellular Ca2+ levels. Considering that hyperphosphorylation of cytoskeletal proteins is related to neurodegeneration it is presumed that the Ca2+-dependent hyperphosphorylation of IF proteins caused by KIC may be involved to the neuropathology of MSUD patients. |
publishDate |
2005 |
dc.date.issued.fl_str_mv |
2005 |
dc.date.accessioned.fl_str_mv |
2021-03-02T04:15:44Z |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/218302 |
dc.identifier.issn.pt_BR.fl_str_mv |
0364-3190 |
dc.identifier.nrb.pt_BR.fl_str_mv |
000527184 |
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0364-3190 000527184 |
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http://hdl.handle.net/10183/218302 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Neurochemical research. New York, NY. Vol. 30, no. 9 ( 2005), p. 1139-1146 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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