Crotamine mediates gene delivery into cells through the binding to heparan sulfate proteoglycans

Detalhes bibliográficos
Autor(a) principal: Nascimento, Fabio Dupart [UNIFESP]
Data de Publicação: 2007
Outros Autores: Hayashi, Mirian Akemi Furuie [UNIFESP], Kerkis, Alexandre, Oliveira, Vitor [UNIFESP], Oliveira, Eduardo B., Radis-Baptista, Gandhi [UNIFESP], Nader, Helena Bonciani [UNIFESP], Yamane, Tetsuo, Tersariol, Ivarne Luis dos Santos [UNIFESP], Kerkis, Irina
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: http://dx.doi.org/10.1074/jbc.M604876200
http://repositorio.unifesp.br/handle/11600/29877
Resumo: Recently we have shown that crotamine, a toxin from the South American rattlesnake Crotalus durissus terrificus venom, belongs to the family of cell-penetrating peptides. Moreover, crotamine was demonstrated to be a marker of centrioles, of cell cycle, and of actively proliferating cells. Herein we show that this toxin at non-toxic concentrations is also capable of binding electrostatically to plasmid DNA forming DNA-peptide complexes whose stabilities overcome the need for chemical conjugation for carrying nucleic acids into cells. Interestingly, crotamine demonstrates cell specificity and targeted delivery of plasmid DNA into actively proliferating cells both in vitro and in vivo, which distinguishes crotamine from other known natural cell-penetrating peptides. the mechanism of crotamine penetration and cargo delivery into cells was also investigated, showing the involvement of heparan sulfate proteoglycans in the uptake phase, which is followed by endocytosis and peptide accumulation within the acidic endosomal vesicles. Finally, the permeabilization of endosomal membranes induced by crotamine results in the leakage of the vesicles contents to the cell cytosol.
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spelling Crotamine mediates gene delivery into cells through the binding to heparan sulfate proteoglycansRecently we have shown that crotamine, a toxin from the South American rattlesnake Crotalus durissus terrificus venom, belongs to the family of cell-penetrating peptides. Moreover, crotamine was demonstrated to be a marker of centrioles, of cell cycle, and of actively proliferating cells. Herein we show that this toxin at non-toxic concentrations is also capable of binding electrostatically to plasmid DNA forming DNA-peptide complexes whose stabilities overcome the need for chemical conjugation for carrying nucleic acids into cells. Interestingly, crotamine demonstrates cell specificity and targeted delivery of plasmid DNA into actively proliferating cells both in vitro and in vivo, which distinguishes crotamine from other known natural cell-penetrating peptides. the mechanism of crotamine penetration and cargo delivery into cells was also investigated, showing the involvement of heparan sulfate proteoglycans in the uptake phase, which is followed by endocytosis and peptide accumulation within the acidic endosomal vesicles. Finally, the permeabilization of endosomal membranes induced by crotamine results in the leakage of the vesicles contents to the cell cytosol.Univ Mogi das Cruzes, Ctr Interdisciplinar Invest Bioquim, BR-08780210 Mogi Das Cruzes, SP, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Bioquim, BR-04044020 São Paulo, BrazilInst Butantan, Ctr Toxinol Aplicada, BR-05503900 São Paulo, BrazilClin & Ctr Pesquisa Reprod Humana Roger Abdelmass, BR-01431000 São Paulo, BrazilUniv Cidade São Paulo, Lab Neurociencias, BR-03071000 São Paulo, BrazilUniv São Paulo, Dept Bioquim & Imunol, BR-14049900 Ribeirao Preto, BrazilUniv Fed Pernambuco, Ctr Ciencias Biol, BR-50732970 Recife, PE, BrazilUniv São Paulo, IPEN CNEN SP, BR-05508000 São Paulo, BrazilInst Butantan, Genet Lab, BR-05503900 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Bioquim, BR-04044020 São Paulo, BrazilWeb of ScienceAmer Soc Biochemistry Molecular Biology IncUniv Mogi das CruzesUniversidade Federal de São Paulo (UNIFESP)Inst ButantanClin & Ctr Pesquisa Reprod Humana Roger AbdelmassUniv Cidade São PauloUniversidade de São Paulo (USP)Universidade Federal de Pernambuco (UFPE)Nascimento, Fabio Dupart [UNIFESP]Hayashi, Mirian Akemi Furuie [UNIFESP]Kerkis, AlexandreOliveira, Vitor [UNIFESP]Oliveira, Eduardo B.Radis-Baptista, Gandhi [UNIFESP]Nader, Helena Bonciani [UNIFESP]Yamane, TetsuoTersariol, Ivarne Luis dos Santos [UNIFESP]Kerkis, Irina2016-01-24T13:48:52Z2016-01-24T13:48:52Z2007-07-20info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion21349-21360http://dx.doi.org/10.1074/jbc.M604876200Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 282, n. 29, p. 21349-21360, 2007.10.1074/jbc.M6048762000021-9258http://repositorio.unifesp.br/handle/11600/29877WOS:000248047500063engJournal of Biological Chemistryinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2016-01-24T11:48:52Zoai:repositorio.unifesp.br/:11600/29877Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652016-01-24T11:48:52Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Crotamine mediates gene delivery into cells through the binding to heparan sulfate proteoglycans
title Crotamine mediates gene delivery into cells through the binding to heparan sulfate proteoglycans
spellingShingle Crotamine mediates gene delivery into cells through the binding to heparan sulfate proteoglycans
Nascimento, Fabio Dupart [UNIFESP]
title_short Crotamine mediates gene delivery into cells through the binding to heparan sulfate proteoglycans
title_full Crotamine mediates gene delivery into cells through the binding to heparan sulfate proteoglycans
title_fullStr Crotamine mediates gene delivery into cells through the binding to heparan sulfate proteoglycans
title_full_unstemmed Crotamine mediates gene delivery into cells through the binding to heparan sulfate proteoglycans
title_sort Crotamine mediates gene delivery into cells through the binding to heparan sulfate proteoglycans
author Nascimento, Fabio Dupart [UNIFESP]
author_facet Nascimento, Fabio Dupart [UNIFESP]
Hayashi, Mirian Akemi Furuie [UNIFESP]
Kerkis, Alexandre
Oliveira, Vitor [UNIFESP]
Oliveira, Eduardo B.
Radis-Baptista, Gandhi [UNIFESP]
Nader, Helena Bonciani [UNIFESP]
Yamane, Tetsuo
Tersariol, Ivarne Luis dos Santos [UNIFESP]
Kerkis, Irina
author_role author
author2 Hayashi, Mirian Akemi Furuie [UNIFESP]
Kerkis, Alexandre
Oliveira, Vitor [UNIFESP]
Oliveira, Eduardo B.
Radis-Baptista, Gandhi [UNIFESP]
Nader, Helena Bonciani [UNIFESP]
Yamane, Tetsuo
Tersariol, Ivarne Luis dos Santos [UNIFESP]
Kerkis, Irina
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Univ Mogi das Cruzes
Universidade Federal de São Paulo (UNIFESP)
Inst Butantan
Clin & Ctr Pesquisa Reprod Humana Roger Abdelmass
Univ Cidade São Paulo
Universidade de São Paulo (USP)
Universidade Federal de Pernambuco (UFPE)
dc.contributor.author.fl_str_mv Nascimento, Fabio Dupart [UNIFESP]
Hayashi, Mirian Akemi Furuie [UNIFESP]
Kerkis, Alexandre
Oliveira, Vitor [UNIFESP]
Oliveira, Eduardo B.
Radis-Baptista, Gandhi [UNIFESP]
Nader, Helena Bonciani [UNIFESP]
Yamane, Tetsuo
Tersariol, Ivarne Luis dos Santos [UNIFESP]
Kerkis, Irina
description Recently we have shown that crotamine, a toxin from the South American rattlesnake Crotalus durissus terrificus venom, belongs to the family of cell-penetrating peptides. Moreover, crotamine was demonstrated to be a marker of centrioles, of cell cycle, and of actively proliferating cells. Herein we show that this toxin at non-toxic concentrations is also capable of binding electrostatically to plasmid DNA forming DNA-peptide complexes whose stabilities overcome the need for chemical conjugation for carrying nucleic acids into cells. Interestingly, crotamine demonstrates cell specificity and targeted delivery of plasmid DNA into actively proliferating cells both in vitro and in vivo, which distinguishes crotamine from other known natural cell-penetrating peptides. the mechanism of crotamine penetration and cargo delivery into cells was also investigated, showing the involvement of heparan sulfate proteoglycans in the uptake phase, which is followed by endocytosis and peptide accumulation within the acidic endosomal vesicles. Finally, the permeabilization of endosomal membranes induced by crotamine results in the leakage of the vesicles contents to the cell cytosol.
publishDate 2007
dc.date.none.fl_str_mv 2007-07-20
2016-01-24T13:48:52Z
2016-01-24T13:48:52Z
dc.type.driver.fl_str_mv 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://dx.doi.org/10.1074/jbc.M604876200
Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 282, n. 29, p. 21349-21360, 2007.
10.1074/jbc.M604876200
0021-9258
http://repositorio.unifesp.br/handle/11600/29877
WOS:000248047500063
url http://dx.doi.org/10.1074/jbc.M604876200
http://repositorio.unifesp.br/handle/11600/29877
identifier_str_mv Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 282, n. 29, p. 21349-21360, 2007.
10.1074/jbc.M604876200
0021-9258
WOS:000248047500063
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal of Biological Chemistry
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 21349-21360
dc.publisher.none.fl_str_mv Amer Soc Biochemistry Molecular Biology Inc
publisher.none.fl_str_mv Amer Soc Biochemistry Molecular Biology Inc
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 biblioteca.csp@unifesp.br
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