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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2003-3-10
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CHUK protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Chuk protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKB protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKE protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ikbkb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ikbke protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9862-8
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:12524423-Adenoviridae,
pubmed-meshheading:12524423-Animals,
pubmed-meshheading:12524423-Apoptosis,
pubmed-meshheading:12524423-Cell Survival,
pubmed-meshheading:12524423-Cells, Cultured,
pubmed-meshheading:12524423-Gene Transfer Techniques,
pubmed-meshheading:12524423-Glucose,
pubmed-meshheading:12524423-Humans,
pubmed-meshheading:12524423-I-kappa B Kinase,
pubmed-meshheading:12524423-Insulin,
pubmed-meshheading:12524423-Islets of Langerhans,
pubmed-meshheading:12524423-Mice,
pubmed-meshheading:12524423-Mice, Inbred BALB C,
pubmed-meshheading:12524423-Microscopy, Fluorescence,
pubmed-meshheading:12524423-NF-kappa B,
pubmed-meshheading:12524423-Peptides,
pubmed-meshheading:12524423-Protein Structure, Tertiary,
pubmed-meshheading:12524423-Protein Transport,
pubmed-meshheading:12524423-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12524423-Recombinant Fusion Proteins,
pubmed-meshheading:12524423-Signal Transduction,
pubmed-meshheading:12524423-Transcription Factor RelA
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pubmed:year |
2003
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pubmed:articleTitle |
Protection of islets by in situ peptide-mediated transduction of the Ikappa B kinase inhibitor Nemo-binding domain peptide.
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pubmed:affiliation |
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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