Crotamine mediates gene delivery into cells through the binding to heparan sulfate proteoglycans
Autor(a) principal: | |
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Data de Publicação: | 2007 |
Outros Autores: | , , , , , , , , |
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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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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1814268423167803392 |