論文

査読有り
2003年1月

Translocation of analogues of the antimicrobial peptides magainin and buforin across human cell membranes

JOURNAL OF BIOLOGICAL CHEMISTRY
  • K Takeshima
  • ,
  • A Chikushi
  • ,
  • KK Lee
  • ,
  • S Yonehara
  • ,
  • K Matsuzaki

278
2
開始ページ
1310
終了ページ
1315
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1074/jcb.M208762200
出版者・発行元
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Cationic antimicrobial peptides play important roles in innate immunity. Compared with extensive studies on peptide-bacteria interactions, little is known about peptide-human cell interactions. Using human cervical carcinoma HeLa and fibroblastic TM12 cells, we investigated the cellular uptake of fluorescent analogues of the two representative antimicrobial peptides magainin 2 and buforin 2 in comparison with the representative Arg-rich cell-penetrating Tat-(47-57) peptide (YGRKKRRQRRR). The dose, time, temperature, and energy dependence of translocation suggested that the three peptides cross cell membranes through different mechanisms. The magainin peptide was internalized within a time scale of tens of minutes. The cooperative concentration dependence of uptake suggested that the peptide forms a pore as an intermediate similar to the observations in model membranes. Furthermore, the translocation was coupled with cytotoxicity, which was larger for tumor HeLa cells. In contrast, the buforin peptide translocated within 10 min by a temperature-independent, less concentration-dependent passive mechanism without showing any significant cytotoxicity at the highest concentration investigated (100 muM). The uptake of the Tat peptide was proportional to the peptide concentration, and the concentration dependence was lost upon ATP depletion. The peptide exhibited a moderate cytotoxicity at higher concentrations. The time course did not show saturation even after 120 min. The buforin peptide, covalently attached to the 28-kDa green fluorescent protein, also entered cells, suggesting a potency of the peptide as a vector for macromolecular delivery into cells. However, the mechanism appeared to be different from that of the parent peptide.

Web of Science ® 被引用回数 : 152

リンク情報
DOI
https://doi.org/10.1074/jcb.M208762200
J-GLOBAL
https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200902254546531809
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/12417587
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000180321900079&DestApp=WOS_CPL

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