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Title: Crotamine mediates gene delivery into cells through the binding to heparan sulfate proteoglycans
Authors: 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
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)
Issue Date: 20-Jul-2007
Publisher: Amer Soc Biochemistry Molecular Biology Inc
Citation: Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 282, n. 29, p. 21349-21360, 2007.
Abstract: 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.
ISSN: 0021-9258
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Appears in Collections:Em verificação - Geral

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