Efficient transduction of 11 poly-arginine peptide in an ischemic lesion of mouse brain

Yuki Gotanda, Fan Yan Wei, Hideki Harada, Keisuke Ohta, Kei Ichiro Nakamura, Kazuhito Tomizawa, Kazuo Ushijima

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Direct intracellular delivery of intact proteins has been successfully achieved by tagging cell-penetrating peptide (CPP), which consists of short positively charged amino acids, such as 11 poly-arginine (11R); however, in vivo delivery of the proteins to the brain has remained challenging because it is unclear whether CPP would enable proteins to cross the blood-brain barrier (BBB). In this study, we conducted an in vivo kinetic study to investigate the efficiency of 11R-mediated peptide delivery in the normal and ischemic brain. The 11R was observed in the microvessels and neurons surrounding the microvessels throughout the brain 1 hour after systemic administration, but the signal of the peptide was faint after 2 hours. In a transient middle cerebral artery occlusion mouse model, 11R was markedly enhanced and remained detectable in the cells on the ipsilateral side for as long as 8 hours after administration compared with the contralateral side. These results suggest that 11R is capable of in vivo delivery to the brain by passing through the BBB. Furthermore, 11R-mediated protein transduction could be used for the delivery of therapeutic molecules in cerebral ischemia.

Original languageEnglish
Pages (from-to)2023-2030
Number of pages8
JournalJournal of Stroke and Cerebrovascular Diseases
Volume23
Issue number8
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

Fingerprint

Arginine
Cell-Penetrating Peptides
Peptides
Brain
Microvessels
Blood-Brain Barrier
Proteins
Middle Cerebral Artery Infarction
Protein Sorting Signals
Brain Ischemia
Neurons
Amino Acids
Therapeutics

Keywords

  • brain
  • ischemia
  • poly-arginine
  • Protein transduction

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery
  • Rehabilitation
  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Efficient transduction of 11 poly-arginine peptide in an ischemic lesion of mouse brain. / Gotanda, Yuki; Wei, Fan Yan; Harada, Hideki; Ohta, Keisuke; Nakamura, Kei Ichiro; Tomizawa, Kazuhito; Ushijima, Kazuo.

In: Journal of Stroke and Cerebrovascular Diseases, Vol. 23, No. 8, 01.01.2014, p. 2023-2030.

Research output: Contribution to journalArticle

Gotanda, Yuki ; Wei, Fan Yan ; Harada, Hideki ; Ohta, Keisuke ; Nakamura, Kei Ichiro ; Tomizawa, Kazuhito ; Ushijima, Kazuo. / Efficient transduction of 11 poly-arginine peptide in an ischemic lesion of mouse brain. In: Journal of Stroke and Cerebrovascular Diseases. 2014 ; Vol. 23, No. 8. pp. 2023-2030.
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