Reduced levels of proteasome products in a mouse striatal cell model of huntington's disease
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1371/journal.pone.0145333 http://hdl.handle.net/11449/168352 |
Resumo: | Huntington's disease is the result of a long polyglutamine tract in the gene encoding huntingtin protein, which in turn causes a large number of cellular changes and ultimately results in neurodegeneration of striatal neurons. Although many theories have been proposed, the precise mechanism by which the polyglutamine expansion causes cellular changes is not certain. Some evidence supports the hypothesis that the long polyglutamine tract inhibits the proteasome, a multiprotein complex involved in protein degradation. However, other studies report normal proteasome function in cells expressing long polyglutamine tracts. The controversy may be due to the methods used to examine proteasome activity in each of the previous studies. In the present study, we measured proteasome function by examining levels of endogenous peptides that are products of proteasome cleavage. Peptide levels were compared among mouse striatal cell lines expressing either 7 glutamines (STHdhQ7/Q7) or 111 glutamines in the huntingtin protein, either heterozygous (STHdhQ7/Q111) or homozygous (STHdhQ111/Q111). Both of the cell lines expressing huntingtin with 111 glutamines showed a large reduction in nearly all of the peptides detected in the cells, relative to levels of these peptides in cells homozygous for 7 glutamines. Treatment of STHdhQ7/Q7 cells with proteasome inhibitors epoxomicin or bortezomib also caused a large reduction in most of these peptides, suggesting that they are products of proteasome-mediated cleavage of cellular proteins. Taken together, these results support the hypothesis that proteasome function is impaired by the expression of huntingtin protein containing long polyglutamine tracts. |
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Reduced levels of proteasome products in a mouse striatal cell model of huntington's diseaseHuntington's disease is the result of a long polyglutamine tract in the gene encoding huntingtin protein, which in turn causes a large number of cellular changes and ultimately results in neurodegeneration of striatal neurons. Although many theories have been proposed, the precise mechanism by which the polyglutamine expansion causes cellular changes is not certain. Some evidence supports the hypothesis that the long polyglutamine tract inhibits the proteasome, a multiprotein complex involved in protein degradation. However, other studies report normal proteasome function in cells expressing long polyglutamine tracts. The controversy may be due to the methods used to examine proteasome activity in each of the previous studies. In the present study, we measured proteasome function by examining levels of endogenous peptides that are products of proteasome cleavage. Peptide levels were compared among mouse striatal cell lines expressing either 7 glutamines (STHdhQ7/Q7) or 111 glutamines in the huntingtin protein, either heterozygous (STHdhQ7/Q111) or homozygous (STHdhQ111/Q111). Both of the cell lines expressing huntingtin with 111 glutamines showed a large reduction in nearly all of the peptides detected in the cells, relative to levels of these peptides in cells homozygous for 7 glutamines. Treatment of STHdhQ7/Q7 cells with proteasome inhibitors epoxomicin or bortezomib also caused a large reduction in most of these peptides, suggesting that they are products of proteasome-mediated cleavage of cellular proteins. Taken together, these results support the hypothesis that proteasome function is impaired by the expression of huntingtin protein containing long polyglutamine tracts.Department of Molecular Pharmacology Albert Einstein College of Medicine, 1300 Morris Park AveSão Paulo State University (UNESP) Experimental Campus on the São Paulo CoastDepartment of Biochemistry Escola Paulista de Medicina Federal University of Sao PauloDepartment of Pharmacology Biomedical Science Institute University of São PauloDepartment of Neuroscience Albert Einstein College of Medicine, 1300 Morris Park AveSão Paulo State University (UNESP) Experimental Campus on the São Paulo CoastAlbert Einstein College of MedicineUniversidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Dasgupta, SayaniFishman, Michael A.Mahallati, HanaCastro, Leandro M. [UNESP]Tashima, Alexandre K.Ferro, Emer S.Fricker, Lloyd D.2018-12-11T16:40:55Z2018-12-11T16:40:55Z2015-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1371/journal.pone.0145333PLoS ONE, v. 10, n. 12, 2015.1932-6203http://hdl.handle.net/11449/16835210.1371/journal.pone.01453332-s2.0-849569427362-s2.0-84956942736.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPLoS ONE1,164info:eu-repo/semantics/openAccess2023-10-15T06:10:11Zoai:repositorio.unesp.br:11449/168352Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-10-15T06:10:11Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Reduced levels of proteasome products in a mouse striatal cell model of huntington's disease |
title |
Reduced levels of proteasome products in a mouse striatal cell model of huntington's disease |
spellingShingle |
Reduced levels of proteasome products in a mouse striatal cell model of huntington's disease Dasgupta, Sayani |
title_short |
Reduced levels of proteasome products in a mouse striatal cell model of huntington's disease |
title_full |
Reduced levels of proteasome products in a mouse striatal cell model of huntington's disease |
title_fullStr |
Reduced levels of proteasome products in a mouse striatal cell model of huntington's disease |
title_full_unstemmed |
Reduced levels of proteasome products in a mouse striatal cell model of huntington's disease |
title_sort |
Reduced levels of proteasome products in a mouse striatal cell model of huntington's disease |
author |
Dasgupta, Sayani |
author_facet |
Dasgupta, Sayani Fishman, Michael A. Mahallati, Hana Castro, Leandro M. [UNESP] Tashima, Alexandre K. Ferro, Emer S. Fricker, Lloyd D. |
author_role |
author |
author2 |
Fishman, Michael A. Mahallati, Hana Castro, Leandro M. [UNESP] Tashima, Alexandre K. Ferro, Emer S. Fricker, Lloyd D. |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Albert Einstein College of Medicine Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Dasgupta, Sayani Fishman, Michael A. Mahallati, Hana Castro, Leandro M. [UNESP] Tashima, Alexandre K. Ferro, Emer S. Fricker, Lloyd D. |
description |
Huntington's disease is the result of a long polyglutamine tract in the gene encoding huntingtin protein, which in turn causes a large number of cellular changes and ultimately results in neurodegeneration of striatal neurons. Although many theories have been proposed, the precise mechanism by which the polyglutamine expansion causes cellular changes is not certain. Some evidence supports the hypothesis that the long polyglutamine tract inhibits the proteasome, a multiprotein complex involved in protein degradation. However, other studies report normal proteasome function in cells expressing long polyglutamine tracts. The controversy may be due to the methods used to examine proteasome activity in each of the previous studies. In the present study, we measured proteasome function by examining levels of endogenous peptides that are products of proteasome cleavage. Peptide levels were compared among mouse striatal cell lines expressing either 7 glutamines (STHdhQ7/Q7) or 111 glutamines in the huntingtin protein, either heterozygous (STHdhQ7/Q111) or homozygous (STHdhQ111/Q111). Both of the cell lines expressing huntingtin with 111 glutamines showed a large reduction in nearly all of the peptides detected in the cells, relative to levels of these peptides in cells homozygous for 7 glutamines. Treatment of STHdhQ7/Q7 cells with proteasome inhibitors epoxomicin or bortezomib also caused a large reduction in most of these peptides, suggesting that they are products of proteasome-mediated cleavage of cellular proteins. Taken together, these results support the hypothesis that proteasome function is impaired by the expression of huntingtin protein containing long polyglutamine tracts. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-12-01 2018-12-11T16:40:55Z 2018-12-11T16:40:55Z |
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.uri.fl_str_mv |
http://dx.doi.org/10.1371/journal.pone.0145333 PLoS ONE, v. 10, n. 12, 2015. 1932-6203 http://hdl.handle.net/11449/168352 10.1371/journal.pone.0145333 2-s2.0-84956942736 2-s2.0-84956942736.pdf |
url |
http://dx.doi.org/10.1371/journal.pone.0145333 http://hdl.handle.net/11449/168352 |
identifier_str_mv |
PLoS ONE, v. 10, n. 12, 2015. 1932-6203 10.1371/journal.pone.0145333 2-s2.0-84956942736 2-s2.0-84956942736.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
PLoS ONE 1,164 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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