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Protection of islets by in situ peptide-mediated transduction of the I kappa B kinase inhibitor nemo-binding domain peptide

Academic Article
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Overview

authors

  • Rehman, K. K.
  • Bertera, S.
  • Bottino, R.
  • Balamurugan, A. N.
  • Mai, J. C.
  • Mi, Z. B.
  • Trucco, M.
  • Robbins, Paul D.

publication date

  • March 2003

journal

  • Journal of Biological Chemistry  Journal

abstract

  • We have previously demonstrated that adenoviral gene transfer of the NF-kappaB inhibitor IkappaB to human islets results in protection from interleukin (IL)-1beta-mediated dysfunction and apoptosis. Here we report that human and mouse islets can be efficiently transduced by a cationic peptide transduction domain (PTD-5) without impairment of islet function. PTD mediated delivery of a peptide inhibitor of the IL-1beta-induced IkappaB kinase (IKK), derived from IKKbeta (NBD; Nemo-binding domain), and completely blocked the detrimental effects of IL-1beta on islet function and NF-kappaB activity, in a similar manner to Ad-IkappaB. We also demonstrate that mouse islets can be transduced in situ by infusion of the transduction peptide through the bile duct prior to isolation, resulting in 40% peptide transduction of the beta-cells. Delivery of the IKK inhibitor transduction fusion peptide (PTD-5-NBD) in situ to mouse islets resulted in improved islet function and viability after isolation. These results demonstrate the feasibility of using PTD-mediated delivery to transiently modify islets in situ to improve their viability and function during isolation, prior to transplantation.

subject areas

  • Adenoviridae
  • Animals
  • Apoptosis
  • Cell Survival
  • Cells, Cultured
  • Gene Transfer Techniques
  • Glucose
  • Humans
  • I-kappa B Kinase
  • Insulin
  • Islets of Langerhans
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Fluorescence
  • NF-kappa B
  • Peptides
  • Protein Structure, Tertiary
  • Protein Transport
  • Protein-Serine-Threonine Kinases
  • Recombinant Fusion Proteins
  • Signal Transduction
  • Transcription Factor RelA
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Identity

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M207700200

PubMed ID

  • 12524423
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Additional Document Info

start page

  • 9862

end page

  • 9868

volume

  • 278

issue

  • 11

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